Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.Dystroglycans: Dystrophin-associated proteins that play role in the formation of a transmembrane link between laminin-2 and DYSTROPHIN. Both the alpha and the beta subtypes of dystroglycan originate via POST-TRANSLATIONAL PROTEIN PROCESSING of a single precursor protein.Neuromuscular Junction: The synapse between a neuron and a muscle.Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.Muscle Fibers, Skeletal: Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.

Globular domains of agrin are functional units that collaborate to induce acetylcholine receptor clustering. (1/304)

Agrin, an extracellular matrix protein involved in neuromuscular junction formation, directs clustering of postsynaptic molecules, including acetylcholine receptors (AChRs). This activity resides entirely in the C-terminal portion of the protein, which consists of three laminin-like globular domains (G-domains: G1, G2 and G3) and four EGF-like repeats. Additionally, alternate mRNA splicing yields G-domain variants G2(0,4) with 0- or 4-amino-acid inserts, and G3(0, 8,11,19) with 0-, 8-, 11- or 19-amino-acid inserts. In order to better understand the contributions of individual domains and alternate splicing to agrin activity, single G-domains and covalently linked pairs of G-domains were expressed as soluble proteins and their AChR clustering activity measured on cultured C2 myotubes. These analyses reveal the following: (1) While only G3(8) exhibits detectable activity by itself, all G-domains studied (G1, G2(0), G2(4), G3(0) and G3(8)) enhance G3(8) activity when physically linked to G3(8). This effect is most pronounced when G2(4) is linked to G3(8) and is independent of the order of the G-domains. (2) The deletion of EGF-like repeats enhances activity. (3) Increasing the physical separation between linked G1 and G3(8) domains produces a significant increase in activity; similar alterations to linked G2 and G3(8) domains are without effect. (4) Clusters induced by two concatenated G3(8) domains are significantly smaller than all other agrin forms studied. These data suggest that agrin G-domains are the functional units which interact independently of their specific organization to yield AChR clustering. G-domain synergism resulting in biological output could be due to physical interactions between G-domains or, alternatively, independent interactions of G-domains with cell surface receptors which require spatially localized coactivation for optimal signal transduction.  (+info)

Constitutively active MuSK is clustered in the absence of agrin and induces ectopic postsynaptic-like membranes in skeletal muscle fibers. (2/304)

In skeletal muscle fibers, neural agrin can direct the accumulation of acetylcholine receptors (AChR) and transcription of AChR subunit genes from the subsynaptic nuclei. Although the receptor tyrosine kinase MuSK is required for AChR clustering, it is less clear whether MuSK regulates gene transcription. To elucidate the role of MuSK in these processes, we constructed a constitutively active MuSK receptor, MuSKneuTMuSK, taking advantage of the spontaneous homodimerization of the transmembrane domain of neuT, an oncogenic variant of the neu/erbB2 receptor. In the extrasynaptic region of innervated muscle fibers, MuSKneuTMuSK formed highly concentrated aggregates that colocalized with AChR clusters. Associated with MuSK-induced AChR clusters was a normal complement of synaptic proteins. Moreover, transcription of the AChR-epsilon subunit gene was increased, albeit via an indirect mechanism by MuSK-induced aggregation of erbB receptors and neuregulin. Although neural agrin was not required, the activity of MuSKneuTMuSK was nevertheless potentiated by ectopic expression of a muscle agrin isoform inactive in AChR clustering. To define the role of the kinase domain in the formation of a postsynaptic-like membrane, a second fusion receptor, neuneuTMuSK, which included the MuSK kinase but not the MuSK extracellular domain, was expressed. Significantly, neuneuTMuSK induced AChR clusters that colocalized with aggregates of endogenous MuSK. Taken together, it was concluded that the MuSK kinase domain is sufficient to initiate the recruitment of additional MuSK receptors, which then develop into highly concentrated aggregates by means of a positive feedback loop to induce a postsynaptic membrane in the absence of neural agrin.  (+info)

Agrin in Alzheimer's disease: altered solubility and abnormal distribution within microvasculature and brain parenchyma. (3/304)

Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with beta-amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to beta-amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.  (+info)

Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction. (4/304)

Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z+) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.  (+info)

Roles of rapsyn and agrin in interaction of postsynaptic proteins with acetylcholine receptors. (5/304)

At the neuromuscular junction, aggregates of acetylcholine receptors (AChRs) are anchored in the muscle membrane by association with rapsyn and other postsynaptic proteins. We have investigated the interactions between the AChR and these proteins in cultured C2 myotubes before and after treatment with agrin, a nerve-derived protein that induces AChRs to cluster. When AChRs were isolated from detergent extracts of untreated C2 myotubes, they were associated with rapsyn and, to a lesser degree, with utrophin, beta-dystroglycan, MuSK, and src-related kinases, but not with syntrophin. Treatment with agrin increased the association of AChRs with MuSK, a receptor tyrosine kinase that forms part of the agrin receptor complex, without affecting other interactions. Analysis of rapsyn-deficient myotubes, which do not form protein clusters in response to agrin, revealed that rapsyn is required for association of the AChR with utrophin and beta-dystroglycan, and for the agrin-induced increase in association with MuSK, but not for constitutive interactions with MuSK and src-related kinases. In rapsyn -/- myotubes, agrin caused normal tyrosine phosphorylation of AChR-associated and total MuSK, whereas phosphorylation of the AChR beta subunit, both constitutive and agrin-induced, was strongly reduced. These results show first that aneural myotubes contain preassembled AChR protein complexes that may function in the assembly of the postsynaptic apparatus, and second that rapsyn, in addition to its role in AChR phosphorylation, mediates selected protein interactions with the AChR and serves as a link between the AChR and the dystrophin/utrophin glycoprotein complex.  (+info)

Evidence of an agrin receptor in cortical neurons. (6/304)

Agrin plays a key role in directing the differentiation of the vertebrate neuromuscular junction. Understanding agrin function at the neuromuscular junction has come via molecular genetic analyses of agrin as well as identification of its receptor and associated signal transduction pathways. Agrin is also expressed by many populations of neurons in brain, but its role remains unknown. Here we show, in cultured cortical neurons, that agrin induces expression of the immediate early gene c-fos in a concentration-dependent and saturable manner, as expected for a signal transduction pathway activated by a cell surface receptor. Agrin is active in cortical neurons at picomolar concentrations, is Ca(2+) dependent, and is inhibited by heparin and staurosporine. Despite marked differences in acetylcholine receptor (AChR)-clustering activity, all alternatively spliced forms of agrin are equally potent inducers of c-fos in cortical neurons. A similar, isoform-independent response to agrin was also observed in cultures prepared from the hippocampus and cerebellum. Only agrin with high AChR-clustering activity was effective in cultured muscle, whereas non-neuronal cells were agrin insensitive. Although consistent with a receptor tyrosine kinase model similar to the muscle-specific kinase-myotube-associated specificity component complex in muscle, our data suggest that CNS neurons express a unique agrin receptor. Evidence that neuronal signal transduction is mediated via an increase in intracellular Ca(2+) means that agrin is well situated to influence important Ca(2+)-dependent functions in brain, including neuronal growth, differentiation, and adaptive changes in gene expression associated with synaptic remodeling.  (+info)

Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializations. (7/304)

Agrin released from motor nerve terminals activates a muscle-specific receptor tyrosine kinase (MuSK) in muscle cells to trigger formation of the skeletal neuromuscular junction. A key step in synaptogenesis is the aggregation of acetylcholine receptors (AChRs) in the postsynaptic membrane, a process that requires the AChR-associated protein, rapsyn. Here, we mapped domains on MuSK necessary for its interactions with agrin and rapsyn. Myotubes from MuSK(-/)- mutant mice form no AChR clusters in response to agrin, but agrin-responsiveness is restored by the introduction of rat MuSK or a Torpedo orthologue. Thus, MuSK(-/)- myotubes provide an assay system for the structure-function analysis of MuSK. Using this system, we found that sequences in or near the first of four extracellular immunoglobulin-like domains in MuSK are required for agrin responsiveness, whereas sequences in or near the fourth immunoglobulin-like domain are required for interaction with rapsyn. Analysis of the cytoplasmic domain revealed that a recognition site for the phosphotyrosine binding domain-containing proteins is essential for MuSK activity, whereas consensus binding sites for the PSD-95/Dlg/ZO-1-like domain-containing proteins and phosphatidylinositol-3-kinase are dispensable. Together, our results indicate that the ectodomain of MuSK mediates both agrin- dependent activation of a complex signal transduction pathway and agrin-independent association of the kinase with other postsynaptic components. These interactions allow MuSK not only to induce a multimolecular AChR-containing complex, but also to localize that complex to a primary scaffold in the postsynaptic membrane.  (+info)

Formation of the neuromuscular junction. Agrin and its unusual receptors. (8/304)

Synapses are essential relay stations for the transmission of information between neurones and other cells. An ordered and tightly regulated formation of these structures is crucial for the functioning of the nervous system. The induction of the intensively studied synapse between nerve and muscle is initiated by the binding of neurone-specific isoforms of the basal membrane protein agrin to receptors on the surface of myotubes. Agrin activates a receptor complex that includes the muscle-specific kinase and most likely additional, yet to be identified, components. Receptor activation leads to the aggregation of acetylcholine receptors (AChR) and other proteins of the postsynaptic apparatus. This activation process has unique features which distinguish it from other receptor tyrosine kinases. In particular, the autophosphorylation of the kinase domain, which usually induces the recruitment of adaptor and signalling molecules, is not sufficient for AChR aggregation. Apparently, interactions of the extracellular domain with unknown components are also required for this process. Agrin binds to a second protein complex on the muscle surface known as the dystrophin-associated glycoprotein complex. This binding forms one end of a molecular link between the extracellular matrix and the cytoskeleton. While many components of the machinery triggering postsynaptic differentiation have now been identified, our picture of the molecular pathway causing the redistribution of synaptic proteins is still incomplete.  (+info)

*Neuromuscular junction

Agrin, a heparin proteoglycan, and MuSK kinase are thought to help stabilize the accumulation of AChR in the central regions of ... In mice which are deficient for either agrin or MuSK, the neuromuscular junction does not form. Further, mice deficient in Dok- ... Upon activation by its ligand agrin, MuSK signals via two proteins called "Dok-7" and "rapsyn", to induce "clustering" of ... "Agrin acts via a MuSK receptor complex". Cell. 85 (4): 513-23. doi:10.1016/S0092-8674(00)81252-0. PMID 8653787. Witzemann V ( ...

*Agrin

The requirement for Agrin and MuSK in the formation of the NMJ was demonstrated primarily by knockout mouse studies. In mice ... Agrin was first identified by the U.J. McMahan laboratory, Stanford University. During development, the growing end of motor ... The nerve secretes agrin, resulting in phosphorylation of the MuSK receptor. It seems that the MuSK receptor recruits casein ... Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during ...

*Laminin

AGRIN; ATRN; ATRNL1; CELSR1; CELSR2; CELSR3; CRELD1; HSPG2; LAMA1; LAMA2; LAMA3; LAMA4; LAMA5; LAMB1; LAMB2; LAMB3; LAMB4; ... AGRIN; CELSR1; CELSR2; CELSR3; CNTNAP1; CNTNAP2; CNTNAP3; CNTNAP3B; CNTNAP4; CNTNAP5; COL11A1; COL11A2; COL12A1; COL14A1; ...

*EGF-like domain

Below is a list of human proteins containing the EGF-like domain: AGC1; AGRIN; AREG; ATRN; ATRNL1; BCAN; BMP1; BTC; C1S; CASPR4 ...

*Olfactory memory

Moberg, Paul J.; Agrin, Rachel; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.; Doty, Richard L. (September 1999). " ...

*Dok-7

May 1996). "Agrin acts via a MuSK receptor complex". Cell. 85 (4): 513-23. doi:10.1016/S0092-8674(00)81252-0. PMID 8653787. ... In mice which are deficient for either agrin or MuSK, the neuromuscular junction does not form. Upon activation by its ligand ... Furthermore, the nerve-derived organizing factor agrin fails to stimulate MuSK activation in muscle cells genetically null for ... agrin, MuSK signals via the proteins called Dok-7 and rapsyn, to induce "clustering" of acetylcholine receptors (AChR). Cell ...

*George Yancopoulos

May 1996). "Agrin acts via a MuSK receptor complex". Cell. 85 (4): 513-23. doi:10.1016/S0092-8674(00)81252-0. PMID 8653787. ...

*Torpedo (genus)

For example, agrin was first isolated from Torpedo. Scribonius Largus, a first century physician, advised the use of a live ...

*Behavior mutation

Also, ennui is very important for agrin function. Ennui is very important in nerve-dependent acetylcholine clustering and the ...

*Development of the nervous system

Agrin induces clustering of AchRs on the muscle surface and synapse formation is disrupted in agrin knockout mice. Agrin ... Agrin appears not to be a central mediator of CNS synapse formation and there is active interest in identifying signals that ... They also showed that the synaptogenic signal is produced by the nerve, and they identified the factor as Agrin. ...

*MuSK protein

It is activated by a nerve-derived proteoglycan called agrin. Upon activation by its ligand agrin, MuSK signals via the ...

*Dystroglycan

The dystroglycan complex is also known to serve as an agrin receptor in muscle, where it may regulate agrin-induced ... Gesemann M, Brancaccio A, Schumacher B, Ruegg MA (Jan 1998). "Agrin is a high-affinity binding protein of dystroglycan in non- ... Actin-binding protein Agrin GRCh38: Ensembl release 89: ENSG00000173402 - Ensembl, May 2017 GRCm38: Ensembl release 89: ... is a functional agrin receptor". Cell. 77 (5): 675-86. doi:10.1016/0092-8674(94)90052-3. PMID 8205617. Ibraghimov-Beskrovnaya O ...

*ITGA7

Burkin DJ, Kim JE, Gu M, Kaufman SJ (2000). "Laminin and alpha7beta1 integrin regulate agrin-induced clustering of ...

*Myasthenia gravis

Other less frequent antibodies are found against LRP4, Agrin and titin proteins. Human leukocyte antigens have been associated ...

*Glomerular basement membrane

Agrin, a protein linked to heparan sulfate basement membrane nephrin Renal corpuscle. GBM is #1. Jarad, G.; Miner, J. H. (2009 ...

*RAPSN

The rapsyn protein interacts directly with the AChRs and plays a vital role in agrin-induced clustering of the AChR. Without ... This pathway consists of agrin, muscle-specific tyrosine kinase (MuSK protein), AChRs and the AChR-clustering protein rapsyn, ... Han H, Noakes PG, Phillips WD (Sep 1999). "Overexpression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in ... "Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein ...

*Markus Rüegg

The agrin gene codes for a family of basal lamina proteins that differ in function and distribution. Neuron 8, 691-699. PMID ... An agrin minigene rescues dystrophic symptoms in a mouse model for congenital muscular dystrophy. Nature 413, 302-307. PMID ... Apoptosis inhibitors and mini-agrin have additive benefits in congenital muscular dystrophy mice. EMBO Mol Med 3, 465-479. PMID ...

*Omigapil

Meinen S, Lin S, Thurnherr R, Erb M, Meier T, Rüegg MA (August 2011). "Apoptosis inhibitors and mini-agrin have additive ... Given that the technology for mini-agrin administration to skeletal muscle in human subjects is not yet available, omigapil is ... Omigapil coupled with mini-agrin overexpression works as a dual treatment that enhances mechanical load bearing ability and ... "Apoptosis inhibitors and mini-agrin have additive benefits in congenital muscular dystrophy mice". EMBO Molecular Medicine. 3 ( ...

*Synaptogenesis

Agrin binds to a muscle-specific kinase (MuSK) receptor in the post-synaptic membrane, and this in turn leads to downstream ... The axon of the motoneuron releases agrin, a proteoglycan that initiates a cascade that eventually leads to AChR association. ... In motor neurons, Wnt-3 works with Agrin to promote growth cone enlargement, axon branching and synaptic vesicle clustering. ... AChR experiences multimerization within the post-synaptic membrane largely due to the signaling molecule Agrin. ...

*INaturalist

Nate Agrin and Ken-ichi Ueda continued work on the site with Sean McGregor, a web developer. In 2011, Ueda began collaboration ... iNaturalist.org began in 2008 as a UC Berkeley School of Information Master's final project of Nate Agrin, Jessica Kline, and ...

*Someone's Coming

https://www.discogs.com/release/924922-Hobo-With-A-Grin/images "Steve Harley - Hobo With A Grin (Vinyl, LP, Album) at Discogs ... https://www.discogs.com/release/924922-Hobo-With-A-Grin/images "Steve Harley - Poetic Justice (CD, Album)". Discogs.com. ...

*Ocellated electric ray

The protein agrin, which concentrates acetylcholine receptors during human embryonic development, was first isolated from this ...

*Congenital myasthenic syndrome

Rapsyn interacts directly with the AChRs and plays a vital role in agrin-induced clustering of the AChR. Without rapsyn, ... This pathway consists of agrin, muscle-specific tyrosine kinase (MuSK), acetylcholine receptors (AChRs) and the AChR-clustering ...

*Neurexin

The encoded proteins are structurally similar to laminin, slit, and agrin, other proteins involved in axon guidance and ...

*CA-125

The C-terminal domain contains multiple extracellular SEA (sea urchin sperm protein, enterokinase, and agrin) modules, a ... enterokinase and agrin) module in cleavage of membrane-tethered mucins". The FEBS Journal. 272 (11): 2901-11. doi:10.1111/j. ...
Agrin is an extracellular matrix protein that directs neuromuscular junction formation. Early signal transduction events in agrin-mediated postsynaptic differentiation include activation of a receptor tyrosine kinase and phosphorylation of acetylcholine receptors (AChRs), but later steps in this pathway are unknown. Here, we have investigated the role of intracellular calcium in agrin-induced AChR clustering on cultured myotubes. Clamping intracellular calcium levels by loading with the fast chelator BAPTA inhibited agrin-induced AChR aggregation. In addition, preexisting AChR aggregates dispersed under these conditions, indicating that the maintenance of AChR clusters is similarly dependent on intracellular calcium fluxes. The decrease in AChR clusters in BAPTA-loaded cells was dose-dependent and reversible, and no change in the number or mobility of AChRs was observed. Clamping intracellular calcium did not block agrin-induced tyrosine phosphorylation of the AChR beta-subunit, indicating that
Agrin, an extracellular matrix-associated protein extracted from synapse-rich tissues, induces the accumulation of acetylcholine receptors (AChRs) and other synaptic components into discrete patches on cultured myotubes. The appearance of agrin-like molecules at neuromuscular junctions suggests that it may direct synaptic organization in vivo. In the present study we examined the role of extracellular matrix components in agrin-induced differentiation. We used immunohistochemical techniques to visualize the spatial and temporal distribution of laminin, a heparan sulfate proteoglycan (HSPG), fibronectin, and type IV collagen on cultured chick myotubes during agrininduced aggregation of AChRs. Myotubes displayed significant amounts of laminin and HSPG, lesser amounts of type IV collagen, and little, if any, fibronectin. Agrin treatment caused cell surface laminin and HSPG to patch, while collagen and fibronectin distributions were generally unaffected. Many of the agrin-induced laminin and HSPG patches
Signaling between nerve and muscle occurs at neuromuscular junctions (NMJs), which consist of specialized and precisely apposed pre- and postsynaptic structures separated by a synaptic cleft (Sanes and Lichtman 1999). Agrin, a heparan sulfate proteoglycan of ∼400-600 kD, is essential for the induction and organization of the postsynaptic structures (McMahan 1990; Gautam et al. 1996; Cohen et al. 1997; Jones et al. 1997; Meier et al. 1997; Rimer et al. 1997). Agrin is synthesized by motor neurons, transported to axon terminals, and released into the synaptic cleft of NMJs, where it binds to the basal lamina (Magill-Solc and McMahan 1988, Magill-Solc and McMahan 1990; Cohen and Godfrey 1992; Reist et al. 1992). Motor neurons express a mixture of agrin isoforms, alternatively spliced at two sites (A and B in chick, y and z in rat) in their COOH-terminal halves (Ruegg et al. 1992; Rupp et al. 1992; Hoch et al. 1993). The neural isoform of agrin containing inserts of four and eight amino acids at ...
At the neuromuscular junction, aggregates of acetylcholine receptors (AChRs) are anchored in the muscle membrane by association with rapsyn and other postsynaptic proteins. We have investigated the interactions between the AChR and these proteins in cultured C2 myotubes before and after treatment with agrin, a nerve-derived protein that induces AChRs to cluster. When AChRs were isolated from detergent extracts of untreated C2 myotubes, they were associated with rapsyn and, to a lesser degree, with utrophin, beta-dystroglycan, MuSK, and src-related kinases, but not with syntrophin. Treatment with agrin increased the association of AChRs with MuSK, a receptor tyrosine kinase that forms part of the agrin receptor complex, without affecting other interactions. Analysis of rapsyn-deficient myotubes, which do not form protein clusters in response to agrin, revealed that rapsyn is required for association of the AChR with utrophin and beta-dystroglycan, and for the agrin-induced increase in association ...
Agrin, a synapse-organizing protein externalized by motor axons at the neuromuscular junction (NMJ), initiates a signaling cascade in muscle cells leading to aggregation of postsynaptic proteins, including acetylcholine receptors (AChRs). We examined whether nitric oxide synthase (NOS) activity is required for agrin-induced aggregation of postsynaptic AChRs at the embryonic NMJ in vivo and in cultured muscle cells. Inhibition of NOS reduced AChR aggregation at embryonic Xenopus NMJs by 50-90%, whereas overexpression of NOS increased AChR aggregate area 2- to 3-fold at these synapses. NOS inhibitors completely blocked agrin-induced AChR aggregation in cultured embryonic muscle cells. Application of NO donors to muscle cells induced AChR clustering in the absence of agrin. Our results indicate that NOS activity is necessary for postsynaptic differentiation of embryonic NMJs and that NOS is a likely participant in the agrin-MuSK signaling pathway of skeletal muscle cells ...
Objectives Osteoarthritis (OA) is a leading cause of disability for which there is no cure. The identification of molecules supporting cartilage homeostasis and regeneration is therefore a major pursuit in musculoskeletal medicine. Agrin is a heparan sulfate proteoglycan which, through binding to low-density lipoprotein receptor-related protein 4 (LRP4), is required for neuromuscular synapse formation. In other tissues, it connects the cytoskeleton to the basement membrane through binding to α-dystroglycan. Prompted by an unexpected expression pattern, we investigated the role and receptor usage of agrin in cartilage. Methods Agrin expression pattern was investigated in human osteoarthritic cartilage and following destabilisation of the medial meniscus in mice. Extracellular matrix (ECM) formation and chondrocyte differentiation was studied in gain and loss of function experiments in vitro in three-dimensional cultures and gain of function in vivo, using an ectopic cartilage formation assay in ...
BACKGROUND: One of the main causes of acute kidney injury (AKI) in patients treated on an intensive care unit (ICU) is sepsis. The identification of new biomarkers indicating the early development and future course of AKI are of utmost medical interest. The C-terminal agrin fragment (CAF) is measurable in blood serum and might reflect kidney function. Therefore, this study evaluates CAF in patients presenting to an internal ICU with severe sepsis or septic shock. Serum levels of CAF are correlated with biomarkers of kidney function, markers of systemic inflammation, and the presence of AKI and renal replacement therapy (RRT ...
Prior studies on dystroglycan support dystroglycan as an agrin-binding protein. More specifically, data suggests that the carbohydrate residues on dystroglycan may be involved in binding to agrin. However, genetic and functional studies on dystroglycans role in agrin-mediated acetylcholine receptor (AChR) clustering remain unclear. Evidence points toward an indirect role for dystroglycan, a role which is important for the aggregation and stabilization of micro-clusters. The question of what regions of dystroglycan are functionally important for its role in agrin-induced AChR clustering is still unanswered. In an attempt to answer this question, we created beta-dystroglycan deletion and point mutants, and expressed these mutants in C2 muscle cells. Next, we assayed transfected myotubes for their responsiveness to agrin by measuring the number of AChR clusters per myotube segment. Last, we characterized a previously unknown protein-lipid interaction for dystroglycan. Our results demonstrate that ...
Glomerular charge selectivity has been attributed to anionic heparan sulfate proteoglycans (HSPGs) in the glomerular basement membrane (GBM). Agrin is the predominant GBM-HSPG, but evidence that it contributes to the charge barrier is lacking, because newborn agrin-deficient mice die from neuromuscular defects. To study agrin in adult kidney, a new conditional allele was used to generate podocyte-specific knockouts. Mutants were viable and displayed no renal histopathology up to 9 months of age. Perlecan, a HSPG normally confined to the mesangium in mature glomeruli, did not appear in the mutant GBM, which lacked heparan sulfate. Moreover, GBM agrin was found to be derived primarily from podocytes. Polyethyleneimine labeling of fetal kidneys revealed anionic sites along both laminae rarae of the GBM that became most prominent along the subepithelial aspect at maturity; labeling was greatly reduced along the subepithelial aspect in agrin-deficient and conditional knockout mice. Despite this
Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. Despite offering poor survival advantage, broad spectrum receptor tyrosine kinase inhibitors are the sole chemotherapeutic treatments for advanced stages of HCC. Hence, there is a pressing clinical need to broaden the scope of HCC treatments through the systematic identification of suitable candidate(s) overexpressed in liver cancer. Therefore, we performed a SILAC based quantitative proteomics of cell surface proteins in HCC lines and identified proteoglycan Agrin to be overexpressed and secreted in HCC. Our systematic cell biological analysis indicated a role of Agrin in maintaining focal adhesion integrity through stimulation of focal adhesion kinase (FAK). We showed that Agrin functions in cellular migration, invasion and tumor growth. However, the exact mechanisms by which Agrins mediates liver tumorigenesis remain unknown. The present study dissects how Agrin mediated signals from the extracellular matrix are ...
Neuromuscular junction (NMJ) assembly is characterized by the clustering and neuronal alignment of acetylcholine receptors (AChRs). In this study we have addressed post-synaptic contributions to assembly that may arise from the NMJ basement membrane with cultured myotubes. We show that the cell surface-binding LG domains of non-neural (muscle) agrin and perlecan promote AChR clustering in the presence of laminin-2. This type of AChR clustering occurs with a several hour lag, requires muscle-specific kinase (MuSK), and is accompanied by tyrosine phosphorylation of MuSK and betaAChR. It also requires conjugation of the agrin or perlecan to laminin together with laminin polymerization. Furthermore, AChR clustering can be mimicked with antibody binding to non-neural agrin, supporting a mechanism of ligand aggregation. Neural agrin, in addition to its unique ability to cluster AChRs through its B/z sequence insert, also exhibits laminin-dependent AChR clustering, the latter enhancing and stabilizing ...
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About Steve Burden. Dr. Burdens laboratory has made significant contributions to our current understanding of the signaling pathways for forming and maintaining neuromuscular synapse. His experiments led to the discovery of the neural signal, Agrin, a secreted, extracellular matrix protein that is necessary to form and stabilize neuromuscular synapses. His laboratory went on to identify Lrp4 as the muscle receptor for Agrin and to discover MuSK, the kinase that associates with Lrp4 and transduces the Agrin signal to stimulate postsynaptic differentiation. Further, his laboratory showed that Lrp4 acts bi-directionally, as Lrp4 not only serves as a muscle receptor for Agrin but also signals in a retrograde manner to motor neurons to control presynaptic differentiation. These studies have led to a good understanding of the signaling events that control synapse formation and provide a basis for understanding how dysfunction of this pathway causes neuromuscular disease and insights into the design ...
Benjamin A. Samuels and Li-Huei Tsai Postsynaptic clusters of acetylcholine receptors (AChR) form at the developing neuromuscular junction (NMJ) prior to apposition by the presynaptic nerve terminal. Subsequently, clusters that are innervated by the nerve terminal become stable, while clusters that are not innervated disperse. It is believed that an important positive signal for stabilization is agrin, but until recently, a signal for dispersion had not been discovered. A recent paper from the lab of Kuo-Fen Lee provides evidence that the Cdk5 kinase plays an essential role in this process (1).. Cdk5 is a small serine/threonine kinase that is primarily active in neurons. However, a report from the lab of Nancy Ip in 2001 first established a potentially important role for Cdk5 in the postsynaptic myotubes of the NMJ by showing it promoted neuregulin-induced transcription of the AChR (2). An abstract from Nancy Ips lab in 2003 also suggested that agrin-induced AChR clusters are significantly ...
Laminin colocalization with AChR aggregates is disrupted on dystroglycan- myotubes. Wild-type (R1) and dystroglycan- myotubes (3C12) were treated overnight with
Research proven purified rabbit polyclonal Neurotrypsin antibody. The synaptic serine protease neurotrypsin is thought to be important for adaptive synaptic processes required for cognitive functions. Truncation or absence of Neurotrypsin causes severe mental retardatio. Neurotrypsin has multiple functions, including axonal outgrowth and maintaining neuronal plasticity. Designed for immunohistochemistry and related applications. IHC image in product description.
Israeli Innovation New research by the Weizmann Institute shows that a molecule found in embryonic cardiac tissue has the ability to promote heart cell regeneration in adults.. Israeli scientists have isolated a molecule that promotes heart cell regeneration, according to the results of a new study published in Nature magazine, a discovery that could offer hope to millions of sufferers of cardiovascular diseases around the world…. Researchers studied a protein called Agrin, common in fetal hearts, which rapidly disappears after birth. They now believe Agrin, which resides in the space between prenatal heart cells, controls the process of cardiomyocyte regeneration.. The scientists extracted Agrin from the hearts of newborn mice, which retain the protein for about a week after birth, and tested it in various environments, to highly encouraging results.. Tags: Israeli Innovation ...
Sigma-Aldrich offers abstracts and full-text articles by [Tohru Tezuka, Akane Inoue, Taisuke Hoshi, Scott D Weatherbee, Robert W Burgess, Ryo Ueta, Yuji Yamanashi].
β-Catenin and Acetylcholine Receptor Clustering. Bin Zhang, Shiwen Luo, Xian-Ping Dong, Xian Zhang, Chunming Liu, Zhenge Luo, Wen-Cheng Xiong, and Lin Mei. (see pages 3968-3973). Its a story that has touched the careers of many neuroscientists: the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction. This week, Zhang et al. add β-catenin to a list of molecular characters that already includes agrin, rapysn, and MuSK (muscle-specific tyrosine kinase). The authors found β-catenin in a two-hybrid screen using rapsyn as bait. They confirmed that the interaction was direct, and that β-catenin coprecipitated with AChR complexes in control myotubes, but not in myotubes derived from rapsyn−/− mice. In a nicely controlled set of experiments, suppression of β-catenin by a short hairpin RNA reduced agrin-induced clustering of AChRs in C2C12 myoblasts. Although β-catenin is multifunctional, its action here did not involve the Wnt signaling pathway. Rather, an interaction ...
Martin Smith, professor of anatomy and neurobiology in the School of Medicine, and his UCI colleagues discovered that agrin -- a protein that directs synapse formation between nerve and muscle cells -- can also inhibit the function of "pumps" that control sodium and potassium levels within cells.. These pumps, called sodium-potassium ATPases -- or sodium pumps, for short -- are especially important in electrically excitable cells, where they provide the basis for electrical impulses, known as action potentials, which are responsible for muscle contraction and signaling between nerve cells in the brain. They do this by pumping sodium out of a cell and pumping potassium in, setting up an electrochemical gradient -- in a sense, turning the cell into a battery. If this activity isnt properly moderated, uncontrollable electrical impulses can be triggered, which is one of the cellular mechanisms behind an epileptic seizure, for instance.. This is where agrin comes into action. The UCI researchers ...
Glomerulonephritis is most commonly an autoimmune-induced inflammatory event wherein infiltration of the kidney by macrophages results in loss of renal function...
A genomic interrogation of homosexuality turns up speculative links between genetic elements and sexual orientation, but researchers say the study is too small to be significant. 6 Comments. ...
We used the loose patch voltage clamp technique and rhodamine-conjugated alpha-bungarotoxin to study the regulation of Na channel (NaCh) and acetylcholine receptor (AChR) distribution on dissociated adult skeletal muscle fibers in culture. The aggregate of AChRs and NaChs normally found in the postsynaptic membrane of these cells gradually fragmented and dispersed from the synaptic region after several days in culture. This dispersal was the result of the collagenase treatment used to dissociate the cells, suggesting that a factor associated with the extracellular matrix was responsible for maintaining the high concentration of AchRs and NaChs at the neuromuscular junction. We tested whether the basal lamina protein agrin, which has been shown to induce the aggregation of AChRs on embryonic myotubes, could similarly influence the distribution of NaChs. By following identified fibers, we found that agrin accelerated both the fragmentation of the endplate AChR cluster into smaller patches as well ...
Botulinum toxin type-A (Btx-A), a powerful therapeutic tool in various medical specialties, requires repeated injections to maintain its effect. Therefore, novel methods to prolong the effective duration time of Btx-A are highly needed. Rats were assigned to three major groups: control group (n = 30), Btx-A group (n = 30), and IGF-1 Ab groups. IGF-1 Ab groups were composed by sub-groups A1-A5 (each has 25 rats) for the subsequent IGF-1Ab dose-effect study. Muscle strength was determined by a survey system for rat lower limbs nerve and muscle function. Muscle-specific receptor tyrosine kinase (MuSK), Insulin-like growth factor binding protein-5 (IGFBP5), and growth-associated protein, 43-kDa (GAP43) were determined by real-time polymerase chain reactions (PCRs) and Western blot. We found that Btx-A decreased the muscle strength, with a paralysis maintained for 70 days. IGF-1Ab prolonged the effective duration time of Btx-A. Real-time PCRs and Western blot showed that IGF-1Ab delayed the increase of
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Antibodies to the muscle-specific receptor tyrosine kinase are involved in the pathogenesis of acetylcholine receptor (ACR) antibody-negative myasthenia gravis. Testing for these antibodies should be considered in the 20 % of patients with clinical symptoms of myasthenia gravis who do not demonstrate antibodies to the ACR.. ...
The neuromuscular junction (NMJ) is a well-studied chemical synapse and has served as a tractable model system to clarify how synapse formation occurs. Proteins on both the presynaptic and postsynaptic sides collaborate to induce the high-density accumulation of acetylcholine receptors (AChRs) at the NMJ. Two opposing pathways work in this process: A dispersing pathway works through acetylcholine and the AChR, and a clustering pathway works through agrin and the transmembrane tyrosine kinase MuSK. The molecular mechanisms underlying these two signaling cascades are beginning to be understood.. ...
The first signs of synapse function The decision to form a synapse The sticky synapse Converting growth cones to presynaptic terminals Receptor clustering and postsynaptic differentiation at the NMJ Agrin is a transynaptic clustering signal at the NMJ Receptor clustering signals in the CNS Scaffold proteins and receptor aggregation in the CNS Innervation increases receptor expression and insertion Synaptic activity regulates receptor density Maturation of transmission and receptor isoform transitions Maturation of transmitter reuptake Short-term plasticity Appearance of synaptic inhibition Is inhibition really inhibitory during development?. Summary 9. Refinement of synaptic connections The early pattern of connections Functional synapses are eliminated Many axonal arborizations are eliminated or refined The Sensory Environment Influences Synaptic Connections Activity Influences Synapse Elimination at the NMJ Synapse refinement is reflected in sensory coding properties Activity contributes to ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
PMCID: PMC3863416. 2012. Buttermore ED, Piochon C. Wallace M, Philpot B, Hansel C, Bhat MA. 2012. Pinceau organization in the cerebellum requires distinct functions of Neurofascin in Purkinje and basket neurons during postnatal development. J Neurosci. 32(14), pp. 4724-4742.. Chen YC, Lin YQ, Banerjee S, Venken K, Li J, Ismat A, Chen K, Duraine L, Bellen HJ, Bhat MA. 2012. Drosophila Neuroligin 2 is required presynaptically and postsynaptically for proper synaptic differentiation and synaptic transmission. J. Neurosci. 32(45), pp. 16018-30.. Coutinho-Budd J, Ghukasyan V, Zylka MJ, and Polleux F. 2012. The F-BAR domains from srGAP1, srGAP2, and srGAP3 differentially regulate membrane deformation. J. Cell Sci. 125(14), pp. 3390-401.. Dumitru, R, Gama, V, Fagan, M, Bower, J, Pevny, L, and Deshmukh, M. 2012. Human embryonic stem cells have constitutively active bax at the golgi and are primed to undergo rapid apoptosis. Mol. Cell. 5, pp. 573-83. Higginbotham H, Eom TY, Mariani LE, Bachleda A, Hirt ...
... has always dreamed big, and tonight he showed off his biggest reverie yet: the fully electric Tesla Semi. Powered by a massive battery and capable of hauling 80,000 pounds, it can ramble 500 miles between charges. Itll even drive itself-on the highway, at least.1 And Musk promises production will start in 2019. The […]. Read More ». ...
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Spinal muscular atrophy (SMA) is a common and often fatal neuromuscular disorder caused by low levels of the Survival Motor Neuron (SMN) protein. Amongst the earliest detectable consequences of SMN deficiency are profound defects of the neuromuscular junctions (NMJs). In model mice these synapses appear disorganized, fail to mature and are characterized by poorly arborized nerve terminals. Given one role of the SMN protein in orchestrating the assembly of spliceosomal snRNP particles and subsequently regulating the alternative splicing of pre-mRNAs, a plausible link between SMN function and the distal neuromuscular SMA phenotype is an incorrectly spliced transcript or transcripts involved in establishing or maintaining NMJ structure. In this study, we explore the effects of one such transcript-Z+Agrin-known to be a critical organizer of the NMJ. We confirm that low SMN protein reduces motor neuronal levels of Z+Agrin. Repletion of this isoform of Agrin in the motor neurons of SMA model mice ...
A variable proportion of patients with generalized myasthenia gravis (MG) have autoantibodies to muscle mass specific tyrosine kinase (MuSK). MuSK expression and/or inhibit the conversation with LRP4. We prepared MuSK IgG, monovalent Fab fragments, IgG1-3 and IgG4 fractions from MuSK-MG plasmas. We asked whether the antibodies caused endocytosis of MuSK in MuSK-transfected cells or if they inhibited binding of LRP4 to MuSK in co-immunoprecipitation experiments. In parallel, we investigated their ability to reduce Ribitol AChR clusters in C2C12 myotubes induced by a) agrin, reflecting neuromuscular development, and b) by Dok7- overexpression, generating AChR clusters that more closely resemble the adult neuromuscular synapse. Total IgG, IgG4 Ribitol or IgG1-3 MuSK antibodies were not endocytosed unless cross-linked by divalent anti-human IgG. MuSK IgG, Fab fragments and IgG4 inhibited the binding of LRP4 to MuSK and reduced agrin-induced Ribitol AChR clustering in C2C12 cells. By contrast, IgG1-3 ...
Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by a breakdown in communication between nerves and muscles, resulting in weakness and rapid fatigue. The muscle weakness associated with myasthenia gravis increases when one is active, but then improves after periods of rest. The degree of muscle weakness varies greatly between individuals.. Myasthenia gravis causes the immune system to produce antibodies that either block or destroy muscles receptor sites for the neurotransmitter acetylcholine. With some receptors blocked, the muscles receive fewer signals and subsequently prevent muscles from contracting, resulting in weakness. Production of the antibodies that block acetylcholine is likely triggered by the thymus, which is found to be abnormally large in people with myasthenia gravis. Sometimes the antibodies, rather than block receptor sites, block the function of a protein called muscle-specific receptor tyrosine kinase, which is involved in creating the ...
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In the current study, the authors show that two strains of AAV, AAV-1 and AAV-2, were effective in transferring the mini-agrin gene to cells in two mouse models. The AAV-1 vector was given by systemic delivery - a single infusion into the abdominal cavity - a method the authors only recently described and which they used for the first time in this study to transfer a therapeutic gene. The AAV-2 vector was delivered locally, given by intramuscular injection to different muscles of the leg. With both approaches, muscle cells were able to assimilate and copy the genetic instructions for making mini-agrin. Once produced, the mini-agrin protein functionally took the place of the laminin alpha-2 protein by binding to the key proteins on either end, thus restoring the cells outside scaffolding and reestablishing the missing link to key structures inside the cell ...
As the β loop motif is sufficient for clustering of chimeric proteins and mutation of β Y390 impairs clustering of intact AChR (Borges and Ferns, 2001), phosphorylation must regulate protein interactions involved in AChR localization. Somewhat unexpectedly, our findings demonstrate that the β loop motif forms a regulated binding site for rapsyn. First, we found that agrin increased rapsyn/AChR association in parallel with β subunit phosphorylation, and that rapsyn was preferentially associated with phosphorylated AChR. Second, rapsyn bound the β loop Y390 region (20 aa) in overlay blots, although binding was not phosphorylation-dependent in this assay. One possible explanation is that Y390 phosphorylation induces a conformational change (Phan-Chan-Du et al., 2003) that promotes rapsyn binding to adjacent residues and this is probably not apparent in overlay blots because most protein is denatured. Alternatively, another muscle protein might form a tertiary complex with rapsyn and the β ...
Since the muscle looked normal, they turned their attention to the motor neuron and got another surprise. Working with Gerald Fischbach, a visiting professor at Rockefeller, the group artificially stimulated the motor axon and found that it was fully able to transmit electrical impulses to secrete its neurotransmitter and cause the muscle to twitch, even though the mice remained completely paralyzed. A more refined picture began to emerge: While Z+ agrin restores the cluster of receptors at the junction, it doesnt restore the ability of the motor neurons to fire ...
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References for Abcams Recombinant human MUSK protein (ab71693). Please let us know if you have used this product in your publication
I cannot speak to the technical issues (a very critical and very interesting take is here) but I wonder where the real gain is (there is a Musk pdf overview of the hyperloop here). You can already fly LA to […]
Renegade immune system. Since the 1970s, its been understood that most MG is due to the immune systems mistaken attack on multiprotein structures called acetylcholine receptors, docking sites on muscle fibers that receive a chemical called acetylcholine from nerve cells. Normally, the presence of acetylcholine causes a muscle fiber to contract, allowing muscle activity to occur.. In most cases of MG, the immune systems inappropriate target is these docking sites. An immune response, in the form of immune system proteins called antibodies, blocks or destroys the acetylcholine receptors, preventing them from receiving the "go" signal from acetylcholine.. In fact, MG is a classic autoimmune disease, a type of disorder in which the body produces an immune response against itself.. These days, its known that the acetylcholine receptors are the most common but not the only target of the immune system in MG. In some people with MG, the target is a protein known as muscle-specific kinase, or MuSK. ...
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This paper focuses on exquisite musk secretion, uses of musk, production of musk, trade of musk, and taxonomy, distribution and conservation of musk deer.
... muscle, skeletal, receptor tyrosine kinase Identifiers Symbol MUSK Entrez 4593 HUGO 7525 OMIM 601296 RefSeq NM_005592 UniProt O15146 Other data
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Elon Musk, the man heading up SpaceX and Tesla, could be launching a new project with the aim of producing an implantable computer-brain interface device. This will be under a new company called Neuralink Corp.
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In this essay Someone called Soter examines the Drake Equation which asks how many technically advanced civilizations exist in our galaxy.. He also looks at the Fermi Paradox which questions why, if there are other technological civilizations nearby, we havent heard from them.. If civilizations exist in our galaxy with level of technology at least equal to our own, we might be able to detect some of them using radio telescopes.. And if civilizations exist with technologies far in advance of our own we might expect them to have colonized millions of habitable worlds in the Milky Way, and even to have visited our own planet.. Yet there is no evidence in the astronomical geological archaeological, or historical records that extraterrestrial civilizations exist or that visitors from other worlds have ever been to Earth.. Does that means as some have concluded that ours is the only civilizations in the galaxy ?. or could there be a natural self regulations mechanism that limits the intensive ...
Extracts of the electric organ of Torpedo californica contain a proteinaceous factor that causes the formation of patches on cultured myotubes at which acetylcholine receptors (AChR), acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) are concentrated. Results of previous experiments indicate that this factor is similar to the molecules in the synaptic basal lamina that direct the aggregation of AChR and AChE at regenerating neuromuscular junctions in vivo. We have purified the active components in the extracts 9,000-fold. mAbs against four different epitopes on the AChR/AChE/BuChE-aggregating molecules each immunoprecipitated four polypeptides from electric organ extracts, with molecular masses of 150, 135, 95, and 70 kD. Gel filtration chromatography of electric organ extracts revealed two peaks of AChR/AChE/BuChE-aggregation activity; one comigrated with the 150-kD polypeptide, the other with the 95-kD polypeptide. The 135- and 70-kD polypeptides did not cause AChR/AChE/BuChE ...
In a study published in the Jan. 30, 2011, advance online edition of Nature Neuroscience, Salk Institute of Biological Studies investigators led by Kuo-Fen Lee, PhD., show that nestin has reason for being in a completely different cell type-muscle tissue.. However, when agrin mutant mice were administered an RNA reagent that literally knocks out nestin expression, the group made a dramatic finding: the pattern of receptor clusters on diaphragm muscle reappeared, reminiscent of synapses of a normal mouse-meaning that getting rid of nestin allows synapses to proceed even in the absence of the stabilizing glue.. This in vivo experiment represents a critical genetic finding, explains Lee. Later, we determined that nestins basic function is to recruit cdk5 and its co-activators to the muscle membrane, leading to cdk5 activation and initiating the dispersion process. Additional experiments confirmed that nestin is expressed on the muscle side of the neuromuscular junction, in other words, in the ...
The present studies were to determine whether the multi-kinase inhibitor sorafenib or its type regorafenib interacted with the ERBB1/ERBB2 inhibitor lapatinib to kill CNS tumor cells. fetal calf serum and 10% (v/v) Non-essential amino acids. All main human being glioblastoma cells were cultured at 37 C (5% (v/v CO2) using RPMI supplemented with 2% 16679-58-6 … Continue reading The present studies were to determine whether the multi-kinase inhibitor sorafenib. ...
Glia. 2015 Jun 29. doi: 10.1002/glia.22878.. Camassa LM, Lunde LK, Hoddevik EH, Stensland M, Boldt HB, De Souza GA, Ottersen OP, Amiry-Moghaddam M.. The brain-blood interface holds the key to our understanding of how cerebral blood flow is regulated and how water and solutes are exchanged between blood and brain. The highly specialized astrocytic membranes that enwrap brain microvessels are salient constituents of the brain-blood interface. These endfoot membranes contain a distinct set of molecules that is anchored to the subendothelial basal lamina forming an endfoot-basal lamina junctional complex. Here we explore the mechanisms underpinning the formation of this complex. By use of a tailor made model system we show that endothelial cells promote AQP4 accumulation by exerting an inductive effect through extracellular matrix components such as agrin, as well as through a direct mechanical interaction with the endfoot processes. Through the compounds they secrete, the endothelial cells also ...
It was only a couple of weeks ago that Tesla CEO and Tony Stark spirit animal Elon Musk unveiled a bonkers concept video outlining his plan for a 30-layer network of traffic tunnels beneath Los Angeles. Now, Musk has released a video on Instagram showing a...
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Tesla CEO Elon Musk proposes a radical new transport system between San Francisco and Los Angeles to speed passengers between the two cities in about half an hour.
The small signalling adaptor protein Dok-7 has recently been reported as an essential protein of the neuromuscular junction (NMJ). Mutations resulting in partial loss of Dok-7 activity cause a distinct limb-girdle subtype of the inherited NMJ disorder congenital myasthenic syndromes (CMSs), whereas complete loss of Dok-7 results in a lethal phenotype in both mice and humans. Here we describe the zebrafish orthologue of Dok-7 and study its in vivo function. Dok-7 deficiency leads to motility defects in zebrafish embryos and larvae. The relative importance of Dok-7 at different stages of NMJ development varies; it is crucial for the earliest step, the formation of acetylcholine receptor (AChR) clusters in the middle of the muscle fibre prior to motor neuron contact. At later stages, presence of Dok-7 is not absolutely essential, as focal and non-focal synapses do form when Dok-7 expression is downregulated. These contacts however are smaller than in the wild-type zebrafish, reminiscent of the ...
The Neuromuscular Synapse Poster© illustrates the connection between a nerve cell and a muscle, where vesicles filled with the neurotransmitter, acetylcholine, fusing with the membrane of the pre-synaptic axon. Following vesicle fusion, the acetylcholine diffuses across the synaptic space to bind to acetylcholine receptors found in the membrane of the muscle cell. Acetylcholinesterase is entangled in the synaptic space, where it breaks down excess neurotransmitter.
Definition of musk in US English - a strong-smelling reddish-brown substance which is secreted by the male musk deer for scent-marking and is an important
Problem: After SCI, the remodeling of axonal circuits is limited resulting in attenuated functional recovery. Target: FGF22 as presynaptic organizer is require …
其實科學界早在1840年代就發現了另一個間隙3是位於肌肉與神經之間的神經肌肉接合點(neuromuscular junction(》雖然對於這個間隙的研究沒有高爾基式的激憤怨懟為其增添戲劇化的色彩3但也充滿了多采多姿的問題與發現3同時也與對於神經元間隙的研究相互啟發 互通有無》明天3七月八日(週四(中午十二點十分3在物理學系(理學大樓(601會議室3香港科技大學生命科學部的彭筱明教授將要引領大家鑽入這個多采多姿的間隙3同時告訴我們如何結合物理與生物來一探究竟》. ...
2015 Elsevier Inc. Myasthenia gravis (MG), the most common autoimmune disease of neuromuscular junction (NMJ), is heterogeneous in terms of pathophysiology, which is determined by the pathogenic antigen of autoantibodies targeting to synaptic proteins at the NMJs. Currently, patients suspected with MG are routinely screened for the presence of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) using a cell-based assay (CBA) that involves the expression of target synaptic membrane protein in heterologous cell lines. However, some autoantibodies may only show reactivity for binding to densely clustered AChR in the physiological conformation, while AChR clustering is known to involve signaling events orchestrated by over a dozen of postsynaptic proteins. To improve the existing serological diagnosis of MG, this study explored the possibility of using the well-established Xenopus primary culture system as a novel CBA for MG. Here, by examining the pathogenic ...
Myasthenia gravis (MG), the most common autoimmune disease of neuromuscular junction (NMJ), is heterogeneous in terms of pathophysiology, which is determined by the pathogenic antigen of autoantibodies targeting to synaptic proteins at the NMJs. Currently, patients suspected with MG are routinely screened for the presence of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) using a cell-based assay (CBA) that involves the expression of target synaptic membrane protein in heterologous cell lines. However, some autoantibodies may only show reactivity for binding to densely clustered AChR in the physiological conformation, while AChR clustering is known to involve signaling events orchestrated by over a dozen of postsynaptic proteins. To improve the existing serological diagnosis of MG, this study explored the possibility of using the well-established Xenopus primary culture system as a novel CBA for MG. Here, by examining the pathogenic effects of four MG human ...
Chemical transmission: There are two classic preparations for the study of chemical transmission at the synapse. One is the vertebrate neuromuscular junction, and the other is the giant synapse of the squid Loligo. These sites have the advantage of being readily accessible for recording by…
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(KudoZ) Italian to English translation of placca neuromuscolare e fondamentale: neuromuscular junction/endplate [Neurotransmitters - Medical (general) (Medical)].
Promotes early disease detection and screening. This resource covers all aspects of the diagnosis and clinical management of patients with diseases of the neuromuscular junction. Breaks down each disease by pathophysiology, clinical presentation, and natural history and course for improved diagnosis and treatment.
Extracellular-signal regulated kinases 1 and 2 (ERK1/2) are the prototypical intracellular mitogen activated protein kinases (MAPK). ERK1/2 are activated by mul...
Another Musk thread! I was thinking for a while to stick it up under some other musk threads around here but then i decided not to. Oh well - I have some questions to the experienced people of basenotes DIY :-) 1. I am anosmic to Galaxolid and can barely smell Cosmone. And i feel bad with it. My friend can smell Galaxolid and Cosmone with no problem and even describe these smells (She finds Galaxolid more womany and Cosmone more manly). I can barely smell some soapy flowers in Cosmone and
While perusing basenotes I noticed in the reviews a lot of guys seem to own multiple frags of different sorts, ranging from light aquatics to heavier musks, and theres quite a bit of diversity out there. I myself currently own 6 different frags, most of them low end: Jovan Musk, Coty Musk, Aqua Velva Musk, Pinauds Lilac Vegetal (just for a stay-at-home aftershave) and Obsession and Truth by Calvin Klein. This small collection is the result of having my work hours modified downward and so
On the heels of the news that Insecure actress Issa Rae and model Ayesha Curry would be joining the Covergirl family, 69-year-old model​ Maye Musk has just been announced, too.
What if we had a computer in our brains? Billionaire entrepreneur Elon Musk is exploring this concept with his latest project, Neuralink.
Identifying mRNAs associated with a synaptogenic calcium-mediated pathway Prof. Brian Ackley, Department of Molecular Biosciences University of Kansas Project dates: 2012-2015 Mentor: Erik Lundquist
Neuromuscular junction, site of chemical communication between a nerve fibre and a muscle cell. The neuromuscular junction is analogous to the synapse between two neurons. A nerve fibre divides into many terminal branches; each terminal ends on a region of muscle fibre called the end plate.
turkeydance shared a new article from Recode about Elon Musk: Hes been warning people about AI for years, and today called it the biggest risk we face as a civilization when he spoke at the National Governors Association Summer Meeting in Rhode Island. Musk then called on the government to proact...
Elon Musk recently gave a Ted Talk in Vancouver where he discussed Tesla, Hyperloop, and his role in President Donald Trumps advisory cabinet.
Jim Stewart of The New York Times discusses the interesting relationship between President Trump and Teslas Elon Musk despite their seemingly opposite agendas.
A photo of the highly anticipated Tesla Model 3 which was pre-ordered by thousands of people was shared by Elon Musk. Thousands of pre-ordering drivers waiting
Resveratrol has been shown to mimic some aspects of caloric restriction and exercise and significantly slows aging of neuromuscular synapses.
Objectives Chondrocytes, the only cells in the articular cartilage, play a pivotal role in osteoarthritis (OA) because they are responsible for maintenance of the extracellular matrix (ECM). Follistatin-like protein 1 (FSTL1) is a secreted protein found in mesenchymal stem cells (MSCs) and cartilage but whose function is unclear. FSTL1 has been shown to modify cell growth and survival. In this work, we sought to determine whether FSTL1 could regulate chondrogenesis and chondrogenic differentiation of MSCs.. ...
Growing evidence shows that alterations occurring at early developmental stages contribute to symptoms manifested in adulthood in the setting of neurodegenerative diseases. Here, we studied the molecular mechanisms causing giant axonal neuropathy (GAN), a severe neurodegenerative disease due to loss-of-function of the gigaxonin-E3 ligase. We showed that gigaxonin governs Sonic Hedgehog (Shh) induction, the developmental pathway patterning the dorso-ventral axis of the neural tube and muscles, by controlling the degradation of the Shh-bound Patched receptor. Similar to Shh inhibition, repression of gigaxonin in zebrafish impaired motor neuron specification and somitogenesis and abolished neuromuscular junction formation and locomotion. Shh signaling was impaired in gigaxonin-null zebrafish and was corrected by both pharmacological activation of the Shh pathway and human gigaxonin, pointing to an evolutionary-conserved mechanism regulating Shh signaling. Gigaxonin-dependent inhibition of Shh ...
In this study, we have found that Fstl1 transcript and protein are upregulated in the myocardium after Akt1 transgene activation. Our studies have also revealed that Fstl1 is a secreted protein and that its overexpression will promote Akt and ERK1/2 signaling in cardiac myocytes and protect cardiac myocytes from hypoxia/reoxygenation-induced apoptosis through activation of these pathways. Conversely, siRNA-mediated knockdown of Fstl1 led to an increase in the frequency of stress-induced apoptosis, and this was associated with a reduction in basal Akt phosphorylation. Fstl1 expression was also upregulated in the heart after pathological stimuli including pressure overload, ischemia/reperfusion, and permanent LAD ligation. Finally, the systemic delivery of Fstl1 protected myocardium from ischemia/reperfusion injury, which was accompanied with a reduction in apoptosis.. A number of lines of evidence suggest that Fstl1 is secreted from cardiac myocytes. Cardiac myocyte cultures display ...
Korpos et al. (1) claim that "limited information exists on the nature of the ECM [extracellular matrix] of the pancreas and, in particular, on the composition of peri-islet capsule," and that they provide the "the first comprehensive analysis of the [ECM] composition of peri-islet capsules.". We dispute the strength of these claims. In mice we originally reported in 2008 that a basement membrane (BM) exists around islets, and eight unique components were identified (type IV collagens α1, α2, laminin α2, β1, γ1, nidogen 1, nidogen 2, perlecan) as well as two composite components (laminin Engelbreth-Holm-Swarm, collagen IV) (2). It was also shown that type IV collagens α3, α4, α5, α6 were not present (2). Korpos et al. (1) were able to find a further three unique components (laminin α4, β2, agrin) and one composite component (laminin 322).. In 2008 in humans (3,4), at least four unique components (laminin α1, α5, β1, γ1) were identified and in their Supplementary Figure 1 staining ...
Buy White Musk® Eau De Toilette from The Body Shop: The White Musk® Eau De Toilette is a blend of our No.1 iconic fragrance: a scented symphony of pure, cruelty-free musk. The perfect light, sensual, floral fragrance. Layer with other White Musk® products to build the fragrance.
Extra-cel-lu-lar matrix pro-teins and adhe-sion pro-teins involved in synapse for-ma-tion, its plas-tic-i-ty and the estab-lish-ment of neu-ronal conec-tiv-i-ty. They also coor-di-nate the pre- and post-sy-nap-tic activ-i-ties and the mat-u-ra-tion of the synapse in the ner-vous sys-tem. To date, how-ev-er their are few datas that high-light mol-e-c-u-lar mecan-isms to which that matri-cials mol-e-cules con-trol the synap-tic devel-op-ment. How Extra-cel-lu-lar matrix pro-teins con-trol the main steps of the synapses for-ma-tion like the axon-al guid-ance, the for-ma-tion and mat-u-ra-tion of the synap-tic con-tact ? In order to answer this ques-tions, the bio-log-i-cal sys-tem used by our team is the neu-ro-mus-cu-lar junc-tion in ver-te-brates. This synapse is an excel-lent mod-èle for the study of synap-to-ge-n-e-sis and has allowed notable steps for-ward in this domain.. ...

Effects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo | JCBEffects of Purified Recombinant Neural and Muscle Agrin on Skeletal Muscle Fibers in Vivo | JCB

Binding of Injected Agrin to the Surface of Muscle Fibers. Neural Agrin.. Neural agrin bound uniformly along the entire length ... Muscle Agrin.. Muscle agrin bound to the surface of innervated and denervated muscle fibers essentially as neural agrin with ... Muscle agrin, however, did not cause aggregation of AChRs. As was the case for neural agrin, nonradioactive muscle agrin ... an excess of nonradioactive muscle agrin did not decrease subsequent binding of neural agrin nor did an excess of neural agrin ...
more infohttp://jcb.rupress.org/content/153/7/1441

The MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses. | Sigma-AldrichThe MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses. | Sigma-Aldrich

Motor neuron-derived agrin activates MuSK via binding to MuSKs coreceptor Lrp4, and genetic defects in agrin underlie a ... The MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses.. [Tohru Tezuka, ... Here, we show that forced expression of Dok-7 in muscle enhanced MuSK activation in mice lacking agrin or Lrp4 and restored ... Thus, it was hypothesized that MuSK needs agrin together with Lrp4 and Dok-7 to achieve sufficient activation to surmount ...
more infohttps://www.sigmaaldrich.com/catalog/papers/25368159

Roles of rapsyn and agrin in interaction of postsynaptic proteins with acetylcholine receptors.  - Zurich Open Repository and...Roles of rapsyn and agrin in interaction of postsynaptic proteins with acetylcholine receptors. - Zurich Open Repository and...

Treatment with agrin increased the association of AChRs with MuSK, a receptor tyrosine kinase that forms part of the agrin ... Treatment with agrin increased the association of AChRs with MuSK, a receptor tyrosine kinase that forms part of the agrin ... Fuhrer, C; Gautam, M; Sugiyama, J E; Hall, Z W (1999). Roles of rapsyn and agrin in interaction of postsynaptic proteins with ... In rapsyn -/- myotubes, agrin caused normal tyrosine phosphorylation of AChR-associated and total MuSK, whereas phosphorylation ...
more infohttp://www.zora.uzh.ch/id/eprint/106/

IDEALS @ Illinois: Structural and Functional Aspects of Dystroglycan During Agrin -Mediated Acetylcholine Receptor Clustering...IDEALS @ Illinois: Structural and Functional Aspects of Dystroglycan During Agrin -Mediated Acetylcholine Receptor Clustering...

The question of what regions of dystroglycan are functionally important for its role in agrin-induced AChR clustering is still ... Next, we assayed transfected myotubes for their responsiveness to agrin by measuring the number of AChR clusters per myotube ... More specifically, data suggests that the carbohydrate residues on dystroglycan may be involved in binding to agrin. However, ... Structural and Functional Aspects of Dystroglycan During Agrin -Mediated Acetylcholine Receptor Clustering at the Mammalian ...
more infohttps://www.ideals.illinois.edu/handle/2142/84805

Most recent papers with the keyword C-terminal agrin fragment | Read by QxMDMost recent papers with the keyword C-terminal agrin fragment | Read by QxMD

C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as ... BACKGROUND: The C-terminal agrin fragment (CAF) is a cleavage product of agrin, the major proteoglycan of the glomerular ... BACKGROUND: C-terminal agrin fragment (CAF), cleavage product of agrin, was previously correlated with kidney function in renal ... C-terminal agrin fragment (CAF, 22 kDa) has been shown to be a promising new rapid biomarker for kidney function. This study ...
more infohttps://www.readbyqxmd.com/keyword/10207

Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in...Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in...

Results Agrin was detected in normal cartilage but was progressively lost in OA. In vitro, agrin knockdown resulted in reduced ... Prompted by an unexpected expression pattern, we investigated the role and receptor usage of agrin in cartilage. Methods Agrin ... Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in ... 2015) Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro ...
more infohttp://epubs.surrey.ac.uk/813981/

Intracellular calcium regulates agrin-induced acetylcholine receptor c by Laura Jalso Megeath and Justin R. Fallon"Intracellular calcium regulates agrin-induced acetylcholine receptor c" by Laura Jalso Megeath and Justin R. Fallon

Finally, the targets of the intracellular calcium are likely to be close to the calcium source, since agrin-induced AChR ... These findings distinguish a novel step in the signal transduction mechanism of agrin and raise the possibility that the ... Here, we have investigated the role of intracellular calcium in agrin-induced AChR clustering on cultured myotubes. Clamping ... Clamping intracellular calcium did not block agrin-induced tyrosine phosphorylation of the AChR beta-subunit, indicating that ...
more infohttps://escholarship.umassmed.edu/oapubs/1180/

Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin - Scott BlystoneMacrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin - Scott Blystone

Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin Blystone, Scott D. Upstate Medical University, Syracuse ... Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin. Blystone, Scott D. / Upstate Medical University. $ ... Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin. Blystone, Scott D. / Upstate Medical University. $ ... Macrophage Infiltration of Renal Tissue via beta-3 Integrins and Agrin. Blystone, Scott D. / Upstate Medical University. $ ...
more infohttp://grantome.com/grant/NIH/R01-DK079884-05

Agrin-induced Reorganization of Extracellular Matrix Components on Cultured Myotubes: Relationship to AChR Aggregation -...Agrin-induced Reorganization of Extracellular Matrix Components on Cultured Myotubes: Relationship to AChR Aggregation -...

Agrin effects myotubes in a dose-dependent manner, although at higher agrin levels the number of AChR patches per myotube ... termed agrin, was identified and characterized (Nitldn et al., 1987). Agrin induces on cultured myotubes dense accumulations of ... Many of the agrin-induced laminin and HSPG patches colocalized with AChR patches, raising the possibility of a causal ... The appearance of agrin-like molecules at neuromuscular junctions suggests that it may direct synaptic organization in vivo. In ...
more infohttps://www.semanticscholar.org/paper/Agrin-induced-Reorganization-of-Extracellular-Matr-Ni/ac4b3f37de0e5c1bcc13ca40f16b18b7ad1e9204

Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering  - edocConjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering - edoc

Neural agrin, in addition to its unique ability to cluster AChRs through its B/z sequence insert, also exhibits laminin- ... We show that the cell surface-binding LG domains of non-neural (muscle) agrin and perlecan promote AChR clustering in the ... Such interactions may contribute to the assembly of aneural AChR clusters that precede neural agrin release as well as affect ... Furthermore, AChR clustering can be mimicked with antibody binding to non-neural agrin, supporting a mechanism of ligand ...
more infohttp://edoc.unibas.ch/2753/

Proteins potential as a regulator of brain activity discoveredProtein's potential as a regulator of brain activity discovered

"The ability of agrin to modulate nerve cell excitability suggests that the agrin-sodium pump interactions can be exploited as a ... This is where agrin comes into action. The UCI researchers observed in laboratory tests that agrin controls the excitability of ... Agrin proteins are also expressed in heart tissue, and Smith notes that sodium pump inhibitors, such as digoxin, are commonly ... Agrin may, therefore, have therapeutic value for the treatment of diseases affecting tissues and organs outside of the brain. ...
more infohttp://www.innovations-report.com/html/reports/life-sciences/report-58248.html

Schwarte RC and Godfrey EW (2004), 
		
		
			Nitric oxide synthase activity is required for ... -
		
		Xenbase Paper
	Schwarte RC and Godfrey EW (2004), Nitric oxide synthase activity is required for ... - Xenbase Paper

Agrin, a synapse-organizing protein externalized by motor axons at the neuromuscular junction (NMJ), initiates a signaling ... Application of NO donors to muscle cells induced AChR clustering in the absence of agrin. Our results indicate that NOS ... NOS inhibitors completely blocked agrin-induced AChR aggregation in cultured embryonic muscle cells. ... activity is required for agrin-induced aggregation of postsynaptic AChRs at the embryonic NMJ in vivo and in cultured muscle ...
more infohttp://www.xenbase.org/literature/article.do?method=display&articleId=3108

Laminin colocalization with AChR aggregates is disrupte | Open-iLaminin colocalization with AChR aggregates is disrupte | Open-i

Wild-type (R1) and dystroglycan- myotubes (3C12) were treated overnight with 500 pM agrin and subsequently fixed and stained ... Wild-type (R1) and dystroglycan- myotubes (3C12) were treated overnight with 500 pM agrin and subsequently fixed and stained ... We show that myotubes differentiated from dystroglycan-/- embryonic stem cells are responsive to agrin, but produce ... We show that myotubes differentiated from dystroglycan-/- embryonic stem cells are responsive to agrin, but produce ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC2195998_JCB0006157.f6&req=4

Plenary SessionsPlenary Sessions

His laboratory went on to identify Lrp4 as the muscle receptor for Agrin and to discover MuSK, the kinase that associates with ... Further, his laboratory showed that Lrp4 acts bi-directionally, as Lrp4 not only serves as a muscle receptor for Agrin but also ... His experiments led to the discovery of the neural signal, Agrin, a secreted, extracellular matrix protein that is necessary to ... Lrp4 and transduces the Agrin signal to stimulate postsynaptic differentiation. ...
more infohttp://www.icnmd2018.org/scientific-program/plenary-sessions/

Agrin Binds BMP2, BMP4 and TGFβ1Agrin Binds BMP2, BMP4 and TGFβ1

We suggest that binding of these TGFβ family members to agrin may have a dual function: agrin may serve as a reservoir for ... Based on analysis of the evolutionary history of agrin we suggest that agrins growth factor binding function is more ancient ... in the case of TGFβ1 Agrin N-term caused a slight increase in activity in reporter assays. Our finding that agrin binds members ... we have explored the interaction of the N-terminal part of rat agrin (Agrin-Nterm) with members of the TGFβ family using ...
more infohttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010758

WikiGenes - AGRN - agrinWikiGenes - AGRN - agrin

The putative agrin receptor binds ligand in a calcium-dependent manner and aggregates during agrin-induced acetylcholine ... Agrin binds alpha-synuclein and modulates alpha-synuclein fibrillation [1].. *Agrin protein binds the amyloidogenic peptide ... Colocalization with agrin binding sites at synapses supports the hypothesis that the alpha3NKA is a neuronal agrin receptor [6] ... An agrin fragment that acts as a competitive antagonist depresses action potential frequency, showing that endogenous agrin ...
more infohttp://www.wikigenes.org/e/gene/e/375790.html

Agrin - WikipediaAgrin - Wikipedia

The requirement for Agrin and MuSK in the formation of the NMJ was demonstrated primarily by knockout mouse studies. In mice ... Agrin was first identified by the U.J. McMahan laboratory, Stanford University. During development, the growing end of motor ... The nerve secretes agrin, resulting in phosphorylation of the MuSK receptor. It seems that the MuSK receptor recruits casein ... Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during ...
more infohttps://en.wikipedia.org/wiki/Agrin

Dr. Rachel Agrin-Silva, Pediatrics - Norwood , MA  | SharecareDr. Rachel Agrin-Silva, Pediatrics - Norwood , MA | Sharecare

She currently practices at Rachel N Agrin-Silva MD and is affiliated with Beth Israel D... ... Rachel Agrin-Silva, MD is a practicing Pediatrician in Norwood, MA. ... Agrin-Silvas Background Bio Rachel Agrin-Silva, MD is a practicing Pediatrician in Norwood, MA. She currently practices at ... Agrin-Silva accepts multiple insurance plans including Aetna, Harvard Pilgrim and Tufts Health Plan. Dr. Agrin-Silva is board ...
more infohttps://www.sharecare.com/doctor/dr-rachel-agrin-silva

Agrin Controls Synaptic Differentiation in Hippocampal Neurons | Journal of NeuroscienceAgrin Controls Synaptic Differentiation in Hippocampal Neurons | Journal of Neuroscience

However, blocking agrin function with agrin-specific antibodies, or reducing agrin expression with antisense oligonucleotides ... 1996) Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin. J Neurosci 16: ... Purified recombinant agrin isoforms (50 pm) (Campanelli et al., 1996) were added as described for the oligonucleotides. Agrin ( ... Agrin mRNA and immunoreactivity can be detected in CNS neurons, where the temporal pattern of expression of agrin parallels ...
more infohttp://www.jneurosci.org/content/20/24/9086

Agrin antibody | acris-antibodies.comAgrin antibody | acris-antibodies.com

Background of Agrin antibody. Kit Component:. - KN212203G1, AGRN gRNA vector 1 in pCas-Guide vector. - KN212203G2, AGRN gRNA ... Western blot analysis of Agrin expression in HEK293T (A); NIH3T3 (B); PC12 (C) whole cell lysates.. *CPA3098-100ul ...
more infohttps://www.acris-antibodies.com/target/agrin-antibody.htm

Agrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles. | JCBAgrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles. | JCB

We also describe anti-agrin staining in nonjunctional regions of muscle. We conclude the following: (a) agrin-like molecules ... Agrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles.. N E Reist, C Magill, U J McMahan ... We found that anti-agrin antibodies intensely stained the synaptic cleft of frog and chicken as well as that of rays, that ... Several lines of evidence have led to the hypothesis that agrin, a protein extracted from the electric organ of Torpedo, is ...
more infohttp://jcb.rupress.org/content/105/6/2457?ijkey=86da6149a6809982b0309495adb7d6dd416ed342&keytype2=tf_ipsecsha

Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture. - Semantic ScholarTransmembrane agrin regulates filopodia in rat hippocampal neurons in culture. - Semantic Scholar

The N-terminal half of agrin was necessary for induction of filopodia, and over-expression of TM-agrin in a neuronal cell line ... Here we demonstrate that agrin positively regulates neuronal filopodia. Over-expression of TM-agrin caused the formation of ... Conversely, suppression of agrin expression by siRNA reduced the number of filopodia. Time lapse analysis indicated that ... By positively regulating filopodia in developing neurons, TM-agrin may influence the pattern of neurite outgrowth and synapse ...
more infohttps://www.semanticscholar.org/paper/Transmembrane-agrin-regulates-filopodia-in-rat-in-McCroskery-Chaudhry/6c3d71057554cb012544d30844f12cc7bd8a5be3

APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice | eLifeAPP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice | eLife

... interact with each other and with a signalling molecule called agrin to influence the development of the neuromuscular junction ... and agrin. (D) Control (lanes 1-3), agrin Z0 (lanes 4-6), agrin Z8 (lanes 7-9), or agrin Z19 (lanes 10-12) containing culture ... C2C12 cells express muscle agrin, which binds to APP as shown in Figure 9. APPs effect could be studied in agrin-/- or KD ... Because APP could bind both muscle and neuronal agrin, an interesting question is if APP acts by aggregating agrin. The ...
more infohttps://elifesciences.org/articles/00220

Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in...Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in...

Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in ... Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in ... Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in ...
more infohttps://ard.bmj.com/content/75/6/1228.info

Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue  - Zurich Open Repository and ArchiveAgrin is a high-affinity binding protein of dystroglycan in non-muscle tissue - Zurich Open Repository and Archive

We found that agrin is most abundant in lung, kidney, and brain. Only a little agrin was detected in skeletal muscle, and no ... We found that agrin is most abundant in lung, kidney, and brain. Only a little agrin was detected in skeletal muscle, and no ... Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue ZORA Maintenance. Maintenance: Thursday, 22 March ... Gesemann, M; Brancaccio, A; Schumacher, B; Ruegg, M A (1998). Agrin is a high-affinity binding protein of dystroglycan in non- ...
more infohttp://www.zora.uzh.ch/id/eprint/124/
  • However, genetic and functional studies on dystroglycan's role in agrin-mediated acetylcholine receptor (AChR) clustering remain unclear. (illinois.edu)
  • The question of what regions of dystroglycan are functionally important for its role in agrin-induced AChR clustering is still unanswered. (illinois.edu)
  • Next, we assayed transfected myotubes for their responsiveness to agrin by measuring the number of AChR clusters per myotube segment. (illinois.edu)
  • Here, we have investigated the role of intracellular calcium in agrin-induced AChR clustering on cultured myotubes. (umassmed.edu)
  • Clamping intracellular calcium levels by loading with the fast chelator BAPTA inhibited agrin-induced AChR aggregation. (umassmed.edu)
  • Clamping intracellular calcium did not block agrin-induced tyrosine phosphorylation of the AChR beta-subunit, indicating that intracellular calcium fluxes are likely to act downstream from or parallel to AChR phosphorylation. (umassmed.edu)
  • Finally, the targets of the intracellular calcium are likely to be close to the calcium source, since agrin-induced AChR clustering was unaffected in cells loaded with EGTA, a slower-binding calcium chelator. (umassmed.edu)
  • Many of the agrin-induced laminin and HSPG patches colocalized with AChR patches, raising the possibility of a causal relationship between matrix patching and AChR accumulations. (semanticscholar.org)
  • However, patching of AChRs (complete within a few hours) preceded that of laminm or HSPG (not complete until 15-20 h), making it unlikely that matrix accumulations initiate AChR patching at agrin-induced sites. (semanticscholar.org)
  • Conversely, when AChR patching was blocked by treatment with anti-AChR antibody mAb 35, agrin was still able to effect patching of laminin and HSPG. (semanticscholar.org)
  • Taken together, these findings suggest that agrin-induced accumulations of AChR and laminin/HSPG are not mechanistically linked. (semanticscholar.org)
  • Several observations suggest that agrin-induced AChR patching occurs through a specific, physiological cellular mechanism. (semanticscholar.org)
  • Agrin effects myotubes in a dose-dependent manner, although at higher agrin levels the number of AChR patches per myotube plateaus off (Godfrey et al. (semanticscholar.org)
  • The MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses. (sigmaaldrich.com)
  • Motor neuron-derived agrin activates MuSK via binding to MuSK's coreceptor Lrp4, and genetic defects in agrin underlie a congenital myasthenic syndrome (an NMJ disorder). (sigmaaldrich.com)
  • However, MuSK-dependent postsynaptic differentiation of NMJs occurs in the absence of a motor neuron, indicating a need for nerve/agrin-independent MuSK activation. (sigmaaldrich.com)
  • Thus, it was hypothesized that MuSK needs agrin together with Lrp4 and Dok-7 to achieve sufficient activation to surmount inhibition by acetylcholine. (sigmaaldrich.com)
  • Here, we show that forced expression of Dok-7 in muscle enhanced MuSK activation in mice lacking agrin or Lrp4 and restored midmuscle NMJ formation in agrin-deficient mice, but not in Lrp4-deficient mice, probably due to the loss of Lrp4-dependent presynaptic differentiation. (sigmaaldrich.com)
  • However, these NMJs in agrin-deficient mice rapidly disappeared after birth, and postsynaptic specializations emerged ectopically throughout myotubes whereas exogenous Dok-7-mediated MuSK activation was maintained. (sigmaaldrich.com)
  • These findings demonstrate that the MuSK activator agrin plays another role essential for the postnatal maintenance, but not for embryonic formation, of NMJs and also for the postnatal, but not prenatal, midmuscle localization of postsynaptic specializations, providing physiological and pathophysiological insight into NMJ homeostasis. (sigmaaldrich.com)
  • Prior studies on dystroglycan support dystroglycan as an agrin-binding protein. (illinois.edu)
  • More specifically, data suggests that the carbohydrate residues on dystroglycan may be involved in binding to agrin. (illinois.edu)
  • Agrin treatment caused cell surface laminin and HSPG to patch, while collagen and fibronectin distributions were generally unaffected. (semanticscholar.org)
  • C-terminal fragment of agrin (CAF), a proteoglycan of the glomerular and tubular basement membrane, have been recently associated with rapid renal function deterioration and proximal tubular dysfunction. (readbyqxmd.com)
  • These findings distinguish a novel step in the signal transduction mechanism of agrin and raise the possibility that the pathways mediating agrin- and activity-driven changes in synaptic architecture could intersect at the level of intracellular calcium fluxes. (umassmed.edu)
  • Although NMJ formation requires agrin under physiological conditions, it is dispensable for NMJ formation experimentally in the absence of the neurotransmitter acetylcholine, which inhibits postsynaptic specialization. (sigmaaldrich.com)
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