TY - JOUR. T1 - Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) is Involved in Proper Dendritic Field Organization. AU - Yamashita, Naoya. AU - Ohshima, Toshio. AU - Nakamura, Fumio. AU - Kolattukudy, Papachan. AU - Honnorat, Jérôme. AU - Mikoshiba, Katsuhiko. AU - Goshima, Yoshio. PY - 2012/1/25. Y1 - 2012/1/25. N2 - Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section. To determine the physiological role of CRMPs in dendritic development, we generated CRMP2 knock-in mutant mice (crmp2ki/ki) in which the Ser residue at 522 was replaced with Ala. Strikingly, the cortical basal dendrites of double mutant ...
Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (−) (10 cases)] and also to metastatic prostate
Sema3A is one of several guidance cues that have been linked to induction of rapid PS and degradation (Campbell and Holt, 2001; Brunet et al., 2005; Wu et al., 2005; Leung et al., 2006; Li et al., 2009). However, the role of PS within the growth cone has been controversial, particularly regarding its necessity for outgrowth and guidance (Eng et al., 1999; Campbell and Holt, 2001; Piper and Holt, 2004; Wu et al., 2005; van Kesteren et al., 2006; Roche et al., 2009). To resolve apparent differences between laboratories we have reinvestigated the role of local PS in Sema3A-induced growth cone collapse. Our data show that three PS inhibitors reduce, but do not eliminate, Sema3A-induced collapse, and both reductions in NGF concentration and increases in Sema3A concentration amplify the PS-independent response. These findings suggest the presence of at least two pathways for Sema3A-induced collapse, which at concentrations ,500 ng/ml produce maximal collapse levels, and which function cooperatively ...
TY - JOUR. T1 - Calpain-mediated generation of a truncated form of collapsing response mediator protein (CRMP-2) promotes neurite degeneration. AU - Koji, Fukui. AU - Ekatherina, Touma. AU - Tatsuro, Koike. AU - Saito, Makoto. PY - 2007/11/3. Y1 - 2007/11/3. M3 - Article. JO - Society for Neuroscience Abstract. JF - Society for Neuroscience Abstract. ER - ...
The collapsin response mediator protein (CRMP) family of intracellular phosphoproteins are predominantly expressed in the nervous system during development. These proteins play important roles in axon formation from neurites, and in neuron guidance, growth, and polarity. CRMP-2 is encoded by the DPYSL2 gene in humans. It is also known as dihydropyrimidinase-like 2 (DRP2), dihydropyrimidinase-related protein 2 (DHPRP2), unc-33-like phosphoprotein 2 (ULIP2), and N2A3. CRMP-2 promotes microtubule assembly and is required for growth cone collapse. It also plays a role in synaptic signaling through interactions with calcium channels. Mutations in the DPYSL2 gene have been implicated in multiple neurological disorders. A hyperphosphorylated form of CRMP-2 may play a key role in the development of Alzheimers disease.. ...
The collapsin response mediator protein (CRMP) family of intracellular phosphoproteins are predominantly expressed in the nervous system during development. These proteins play important roles in axon formation from neurites, and in neuron guidance, growth, and polarity. CRMP-2 is encoded by the DPYSL2 gene in humans. It is also known as dihydropyrimidinase-like 2 (DRP2), dihydropyrimidinase-related protein 2 (DHPRP2), unc-33-like phosphoprotein 2 (ULIP2), and N2A3. CRMP-2 promotes microtubule assembly and is required for growth cone collapse. It also plays a role in synaptic signaling through interactions with calcium channels. Mutations in the DPYSL2 gene have been implicated in multiple neurological disorders. A hyperphosphorylated form of CRMP-2 may play a key role in the development of Alzheimers disease.. ...
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression
Aging is the greatest risk factor for developing neurodegenerative diseases, which are associated with diminished neurotransmission as well as neuronal structure and function. However, several traits seemingly evolved to avert or delay age-related deterioration in the brain of the longest-lived rodent, the naked mole-rat (NMR). The NMR remarkably also exhibits negligible senescence, maintaining an extended healthspan for ~75 % of its life span. Using a proteomic approach, statistically significant changes with age in expression and/or phosphorylation levels of proteins associated with neurite outgrowth and neurotransmission were identified in the brain of the NMR and include: cofilin-1; collapsin response mediator protein 2; actin depolymerizing factor; spectrin alpha chain; septin-7; syntaxin-binding protein 1; synapsin-2 isoform IIB; and dynamin 1 ...
Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Collapsin response mediator protein 3 increases the dendritic arborization of is vidalista 10 generic cialis buy online hippocampal neurons. Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. A ...
Clone REA626 recognizes the human plexin-B2 antigen, a single-pass type I membrane protein, which belongs to the semaphorin receptor family, B subfamily. Plexin-B2 is expressed in the nervous system and on other cells including cells of the immune system. It is expressed on T cells and T cell-dependent germinal center B cells. Expression is also found on macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. Plexin-B2 plays an important role in cell-cell signaling, axon guidance, invasive growth, and cell migration. It has several semaphorin ligands including semaphorin-3E, semaphorin-4A, semaphorin-4C, and semaphorin-4D (CD100). Binding to class 4 semaphorins promotes the downstream activation of RHOA and phosphorylation of ERBB2. During skin damage repairs, CD100 interacts with plexin-B2 on γδ T cells to play a role in the healing process. Additional information: Clone REA626 displays negligible binding to Fc receptors. - USA
Title: Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?. VOLUME: 6 ISSUE: 3. Author(s):M. P.M. Soutar, P. Thornhill, A. R. Cole and C. Sutherland. Affiliation:Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, United Kingdom.. Abstract: Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer s disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal ...
TY - JOUR. T1 - Integration of repulsive guidance cues generates avascular zones that shape mammalian blood vessels. AU - Meadows, Stryder M.. AU - Fletcher, Peter J.. AU - Moran, Carlos. AU - Xu, Ke. AU - Neufeld, Gera. AU - Chauvet, Sophie. AU - Mann, Fanny. AU - Krieg, Paul A. AU - Cleaver, Ondine. PY - 2012/1/6. Y1 - 2012/1/6. N2 - Rationale: Positive signals, such as vascular endothelial growth factor, direct endothelial cells (ECs) to specific locations during blood vessel formation. Less is known about repulsive signal contribution to shaping vessels. Recently, "neuronal guidance cues" have been shown to influence EC behavior, particularly in directing sprouting angiogenesis by repelling ECs. However, their role during de novo blood vessel formation remains unexplored. Objective: To identify signals that guide and pattern the first mammalian blood vessels. Methods and Results: Using genetic mouse models, we show that blood vessels are sculpted through the generation of stereotyped ...
DRP-2, also known as collapsin response mediator protein-2 (CRMP-2), is expressed at high levels in the developing nervous system and plays a critical…
Regenerative coordination and remodeling of the intramuscular motoneuron network and neuromuscular connections are critical for restoring skeletal muscle function and physiological properties. The regulatory mechanisms of such coordination remain unclear, although both attractive and repulsive axon guidance molecules may be involved in the signaling pathway. Here we show that expression of a neural secreted chemorepellent semaphorin 3A (Sema3A) is remarkably upregulated in satellite cells of resident myogenic stem cells that are positioned beneath the basal lamina of mature muscle fibers, when treated with hepatocyte growth factor (HGF), established as an essential cue in muscle fiber growth and regeneration. When satellite cells were treated with HGF in primary cultures of cells or muscle fibers, Sema3A message and protein were upregulated as revealed by reverse transcription-polymerase chain reaction and immunochemical studies. Other growth factors had no inductive effect except for a slight ...
Chemorepulsion is the directional movement of a cell away from a substance. Of the two directional varieties of chemotaxis, chemoattraction has been studied to a much greater extent. Only recently have the key components of the chemorepulsive pathway been elucidated. The exact mechanism is still being investigated, and its constituents are currently being explored as likely candidates for immunotherapies. The mechanism of the chemorepulsion of immune cells was first acknowledged by medical researchers at the Massachusetts General Hospital in Boston in early 2002. The phenomenon was originally referred to as "reverse chemotaxis," and later, "fugetaxis" (derived from the Latin words fugere, to flee from; and taxis, movement). For a time, the words were used interchangeably before being replaced almost exclusively by "chemorepulsion." While "chemorepulsion" applies to all cell types, the term "immunorepulsion" is gaining momentum as a more specific term that only applies to hematopoietic blood cell ...
Post-mitotic neurons in the developing cortex migrate along radial glial fibers to the proper location in the cortical plate and form the layered structure. Here we report that the radial migration of rat layer II/III cortical neurons requires the guidance of an extracellular diffusible factor Semaphorin-3A (Sema3A). Sema3A is expressed in a descending gradient across the cortical layers, whereas its receptor neuropilin-1 (NP1) is expressed at a high level in migrating neurons. Using in utero eletroporation to down-regulate or conditional knockout of NP1 in newborn cortical neurons impeded their radial migration by disrupting their radial orientation during migration without altering their cell fate. Studies in cultured cortical slices further showed the requirement of the endogenous gradient of Sema3A for the proper migration of newborn neurons. Finally, transwell chemotaxis assays showed that isolated newborn neurons were attracted by Sema3A. Thus, Sema3A may serve as a chemoattractive ...
This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016 ...
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MPLPPRSLQVLLLLLLLLLLLPGMWAEAGLPRAGGGSQPPFRTFSASDWGLTHLVVHEQTGEVYVGAVNR 1 - 70 IYKLSGNLTLLRAHVTGPVEDNEKCYPPPSVQSCPHGLGSTDNVNKLLLLDYAANRLLACGSASQGICQF 71 - 140 LRLDDLFKLGEPHHRKEHYLSSVQEAGSMAGVLIAGPPGQGQAKLFVGTPIDGKSEYFPTLSSRRLMANE 141 - 210 EDADMFGFVYQDEFVSSQLKIPSDTLSKFPAFDIYYVYSFRSEQFVYYLTLQLDTQLTSPDAAGEHFFTS 211 - 280 KIVRLCVDDPKFYSYVEFPIGCEQAGVEYRLVQDAYLSRPGRALAHQLGLAEDEDVLFTVFAQGQKNRVK 281 - 350 PPKESALCLFTLRAIKEKIKERIQSCYRGEGKLSLPWLLNKELGCINSPLQIDDDFCGQDFNQPLGGTVT 351 - 420 IEGTPLFVDKDDGLTAVAAYDYRGRTVVFAGTRSGRIRKILVDLSNPGGRPALAYESVVAQEGSPILRDL 421 - 490 VLSPNHQYLYAMTEKQVTRVPVESCVQYTSCELCLGSRDPHCGWCVLHSICSRRDACERADEPQRFAADL 491 - 560 LQCVQLTVQPRNVSVTMSQVPLVLQAWNVPDLSAGVNCSFEDFTESESVLEDGRIHCRSPSAREVAPITR 561 - 630 GQGDQRVVKLYLKSKETGKKFASVDFVFYNCSVHQSCLSCVNGSFPCHWCKYRHVCTHNVADCAFLEGRV 631 - 700 NVSEDCPQILPSTQIYVPVGVVKPITLAARNLPQPQSGQRGYECLFHIPGSPARVTALRFNSSSLQCQNS 701 - 770 SYSYEGNDVSDLPVNLSVVWNGNFVIDNPQNIQAHLYKCPALRESCGLCLKADPRFECGWCVAERRCSLR 771 - 840 ...
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Background: Dental trigeminal axon elongation, navigation and patterning occur in a controlled manner that is intimately linked to tooth shape formation and cell differentiation. Development of tooth results from sequential and reciprocal molecular interactions between epithelial and mesenchymal tissues. Semaphorin family of secreted and membrane-bound axonal growth cone guiding molecules regulates the development of the nervous system and also serves important non-neuronal functions. Many Semaphorins are expressed in the developing tooth germ and there is evidence that Semaphorin signalling regulates tooth innervation.. Objective: To investigate mRNA expression of class 4 semaphorins and their PlexinB receptors in the developing mouse mandibular first molar, and to study further functions of Sema3A during odontogenesis.. Materials and methods: Transgenic Sema3A-deficient mice in C57BL/6 and CD1 background as well as NMRI mice were used. In situ hybridization and immunohistochemistry was ...
TY - JOUR. T1 - Transmembrane semaphorins. T2 - Multimodal signaling cues in development and cancer. AU - Gurrapu, Sreeharsha. AU - Tamagnone, Luca. PY - 2016. Y1 - 2016. N2 - Semaphorins constitute a large family of membrane-bound and secreted proteins that provide guidance cues for axon pathfinding and cell migration. Although initially discovered as repelling cues for axons in nervous system, they have been found to regulate cell adhesion and motility, angiogenesis, immune function and tumor progression. Notably, semaphorins are bifunctional cues and for instance can mediate both repulsive and attractive functions in different contexts. While many studies focused so far on the function of secreted family members, class 1 semaphorins in invertebrates and class 4, 5 and 6 in vertebrate species comprise around 14 transmembrane semaphorin molecules with emerging functional relevance. These can signal in juxtacrine, paracrine and autocrine fashion, hence mediating long and short range repulsive ...
Semaphorin is a large family of proteins that are involved in cell migration control and axonal growth cues (Figure 2.) Some of these proteins can promote chemo cell to cell communication, either repulsive or attractive [10]. An example of this would be Semaphorin 3A; it is a secretory protein of the Semaphorin family [10]. Semaphorin 3A can be secreted by macrophages and OPC. It binds on to the Sema receptor NP-1; exerts it negative cue effects on OPC migration and differentiation. Semaphorin 3A is also involved in peripheral axon growth and regulating the trajectory of neurons [6]. In MS lesions, this receptor is highly expressed in the OPC especially at low inflammation stages [2]. Therefore, Semaphorin 3A acts as a regulator that inhibits OPC differentiation in the feedback loop. Evidence establishes that Semaphorin inhibits CNS myelination in vivo [2]. A possible solution involves drugs that target the Semaphorin 3A signaling, such as RhoA; a signaling effector for Semaphorin 3A [10]. By ...
Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many maligant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell cycle arrest in the G2 phase. Additionally, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexin B2-dependent manner. In conclusion, SEMA4C expression in breast cancer ...
Background: Generally, Semaphorins are secretary or transmembrane-bound molecules that act as axon guidance cues in the nervous system. Recent research showed increased expression of semaphorin 3C correlates with cancers that possess higher invasive and metastatic characteristics. For example, in breast cancer, inhibition of semaphorin 3C reduces adhesion and invasion. The aim of this study was to evaluate a possibility that semaphorin 3C might be a new prognostic marker in colorectal cancer.. Material and methods: We used two cohorts. Cohort 1 was the 192 patients with colorectal cancer resected surgically between 2009 and 2010. We used GSE 14333 dataset as Cohort 2 which included 226 patients with the colorectal cancer. In each cohorts, we divided the patients in to the two groups i.e., high or low semaphorin 3C expression group using receiver operating characteristic (ROC) curve based on the information of the recurrence of colorectal cancer. Disease-free-survival (DFS) rates were calculated ...
Excessive neovascularization of atherosclerotic lesions increases plaque vulnerability and the susceptibility to rupture. Semaphorin 7A (Sema7A), a semaphorin family member, was recently reported to promote atherosclerotic plaque formation by mediating d-flow-induced endothelial phenotypic change and leukocyte adhesion. To extend our understanding of the proatherogenic role of Sema7A, we investigated the role of endothelial Sema7A in angiogenesis and atherosclerotic neovascularization. Sema7A overexpression in human umbilical vein endothelial cells (HUVECs) significantly upregulated VEGFA/VEGFR2 and promoted cell migration and angiogenesis. This enhancing effect was eliminated by the blockage of Sema7A receptor, β1 integrin. Inhibition of FAK or ERK1/2 downstream of β1 integrin signaling significantly inhibited cell migration and angiogenesis via ROCK (Rho-associated coiled forming protein kinase) and MYPT (myosin phosphatase targeting subunit), which are responsible for actin polymerization.
During development, neurons are guided by multiple guidance molecules and their receptors, but how developing neurons integrate these different guidance cues to form neural circuits is unclear. Alex Kolodkins team has been examining the roles of plexins - receptors for the semaphorin guidance cues-in the developing Drosophila nervous system. On p. 2125, these researchers report important new insights into how the multiple components of the semaphorin system interact by showing that the two fly plexins (PlexA and PlexB) have both distinct and overlapping functions in central and peripheral axon pathfinding. Their observation that PlexA and PlexB physically associate in vivo and can use common downstream signalling pathways provides an explanation for their overlapping functions. The researchers discovery that PlexB is a receptor for the secreted semaphorin Sema-2a-PlexA is a receptor for the transmembrane semaphorin Sema-1a-suggests that the distinct roles of the two plexins in axon pathfinding ...
The molecular mechanism by which cAMP mediates PI(3,4,5)P3 accumulation upgradient in D. discoideum cells has been well described. PI3K is activated and enriched upgradient in the cell, whereas the PI(3,4,5)P3-degrading enzyme PTEN strongly localizes downgradient in the cell (Funamoto et al., 2002; Iijima and Devreotes, 2002). PTEN has been demonstrated to bind to phosphatidylinositol-3,4,5-trisphosphate (PI[4,5]P2), suggesting that PI(4,5)P2 is depleted upgradient in the cell (Iijima et al., 2004). This depletion of PI(4,5)P2 could be induced by several nonexclusive methods, such as the observed conversion of PI(4,5)P2 to PI(3,4,5)P3 upgradient by PI3K (Funamoto et al., 2002; Huang et al., 2003), but also by the conversion of PI(4,5)P2 to Ins(1,4,5)P3 and DAG by PLC, which is known to be activated by cAMP (Drayer and van Haastert, 1992; Bominaar et al., 1994). We propose a mechanism by which 8CPT-cAMP could revert the polarity of chemotactic sensing that is based on the observation that cAMP ...
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Semaphorins are a family of cell surface and secreted proteins that are conserved from insects to humans. Members of this family of proteins are…
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Background: Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development of NP. Results: The presence of autoantibodies to GFAP (GFAPab) and CRMP2 (CRMP2ab) and their correlation to the development of NP was evaluated. GFAPab was present in 21 of 38 (55%) acute SCI, 34 of 80 (43%) chronic SCI. CRMP2ab was present in 8/35 (23%) acute SCI patient plasma samples. Complement
TY - JOUR. T1 - Further insights into the antinociceptive potential of a peptide disrupting the N-type calcium channel-CRMP-2 signaling complex. AU - Wilson, Sarah M.. AU - Brittain, Joel M.. AU - Piekarz, Andrew D.. AU - Ballard, Carrie J.. AU - Ripsch, Matthew S.. AU - Cummins, Theodore R.. AU - Hurley, Joyce H.. AU - Khanna, May. AU - Hammes, Nathan M.. AU - Samuels, Brian C.. AU - White, Fletcher A.. AU - Khanna, Rajesh. PY - 2011/1/1. Y1 - 2011/1/1. N2 - The N-type voltage-gated calcium channel (Ca v2.2) has gained immense prominence in the treatment of chronic pain. While decreased channel function is ultimately anti-nociceptive, directly targeting the channel can lead to multiple adverse side effects. Targeting modulators of channel activity may facilitate improved analgesic properties associated with channel block and a broader therapeutic window. A novel interaction between Ca v2.2 and collapsin response mediator protein 2 (CRMP-2) positively regulates channel function by increasing ...
Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures
In this study, we demonstrate that Shh protein induces macropinocytosis in the axons, through activation of a noncanonical signaling pathway. Rho GTPase and nonmuscle myosin II activities were rapidly increased during the treatment of Shh. Macropinocytosis induced by Shh was observed to occur rapidly in the growth cones and was further characterized as independent of clathrin and PI3K but dependent on dynamin and myosin II activities. Inhibitors of macropinocytosis abolished growth cone collapse and repulsive axon turning induced by high Shh, and pharmacologically increased macropinocytosis correlated with growth cone collapse and axon repulsive turning. These results support that macropinocytosis-mediated membrane trafficking is essential for chemorepulsive axon guidance.. Although the correlation of macropinocytosis and axon growth cone collapse has been reported by previous studies (Fournier et al., 2000; Jurney et al., 2002), our study provides the first functional evidence that ...
Morphogenesis in animals involves specific changes in cell shape and position. Several external signals have been identified to modulate the morphology and motility of cells by regulating various cellular properties such as adhesion and cytoskeletal organization. Members of the semaphorin protein family have been implicated as extrinsic guidance cues during the development of the nervous systems (Raper, 2000).. The semaphorin family comprises a large number of secreted and transmembrane proteins classified into seven classes; class 1 and 2 in invertebrates and class 3 to 7 in vertebrates, all characterized by the signature sema domain of 500 amino acid residues (The Semaphorin Nomenclature Committee, 1999). Vertebrate sema3A/collapsin, a founding member of the semaphorin family, was first identified as a potent chemorepellant for growing axons in vitro (Luo et al., 1993). Sema3A collapses growth cones of a subset of neurons by reorganizing their cytoskeleton (Fan et al., 1993; Fan and Raper, ...
Semaphorins are very versatile. Their discovery was in regards to axon guidance in the limb buds of grasshoppers in 1992, but since then, it has been discovered that semaphorins have a role in many processes. They not only guide axons in development, but also have major roles in immune function (classes 4, 6, and 7) and the development of bones. Class 3 semaphorins are one of the most versatile semaphorin classes, in which Sema3a is the most studied. During development, semaphorins and their receptors may be involved in the sorting of pools of motor neurons and the modulation of pathfinding for afferent and efferent axons from and to these pools.[5] For instance, Sema3a repels axons from the dorsal root ganglia, facial nerves, vagal nerves, olfactory-sensory, cortical nerves, hippocampal nerves and cerebellar nerves. Class 3 semaphorins have an important function after traumatic central nervous system injuries, such as spinal cord injury. They regulate neuronal and non-neuronal cells associated ...
From NCBI Gene:. Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]. From UniProt: ...
MicroRNAs (miRNAs) action seeing that transcriptional government bodies and play pivotal assignments in carcinogenesis. miRNAs had been up-regulated on treatment with 5-aza-2′-deoxycytidine in a GC cell series. The TargetScan miRNA 1404-19-9 focus on data source forecasted that some of these miRNAs possess common focus on genetics. We also known to the GEO data source for reflection of these common focus on genetics in individual GCs, which might end up being related to gastric carcinogenesis. In this scholarly study, we examined two miRNA combos, miR-224 and -452, and -340 and miR-181c. Over-expression of both miRNA combos down-regulated their focus on genetics, and and and (dihydropyrimidinase-like 2, known as collapsing response mediator proteins 2 also, by miR-224, -452, -181c, -152 and -340, and (methyl CpG presenting proteins 2) by miR-181c and -340, respectively (Amount 3). Amount 2 MSP evaluation of miR-224/?340 in GC, CRC cell lines and normal tummy. Amount 3 A diagram of the romantic ...
ABSTRACT Semaphorin-3A (Sema3A) regulates tumor angiogenesis, but its role in modulating anti-tumor immunity is unclear. We demonstrate that Sema3A secreted within the tumor microenvironment (TME) suppresses tumor-specific CD8+ T cell function via Neuropilin-1 (NRP1), a receptor that is upregulated upon activation with T cells cognate antigen. Sema3A inhibits T cell migration, assembly of the immunological synapse, and tumor killing. It achieves these functional effects through hyper-activating the acto-myosin system in T cells leading to cellular paralysis. Finally, using a clear cell renal cell carcinoma patient cohort, we demonstrate that human tumor-specific CD8+ T cells express NRP1 and are trapped in Sema3A rich regions of tumors. Our study establishes Sema3A as a potent inhibitor of anti-tumor immunity.
A scheme for PI(3,4,5)P3-mediated chemotaxis reversal by 8CPT-cAMP consists of three parts (Fig. 4). The basis is a PLC/PI(4,5)P2 polarity switch. In D. discoideum, PLC is regulated by the activating Gα2 and inhibitory Gα1, which, in a gradient of attractant or repellent, will determine the polarity of the PI(4,5)P2 gradient. The attractant cAMP shows predominant activation of PLC, leading to lower PI(4,5)P2 levels upgradient, while the repellent 8CPT-cAMP inhibits PLC, leading to higher PI(4,5)P2 levels upgradient. The resulting gradients of PI(4,5)P2 and colocalized PTEN mediate opposite gradients of PI(3,4,5)P3, leading to the localized polymerization of actin. The gradients of localized PTEN and PI3K are stabilized because PTEN accumulates at the site of its product PI(4,5)P2, whereas PI3K accumulates at sites of its effector, PI(3,4,5)P3-induced F-actin. This mutually spatial exclusion of PI3K and PTEN will result in symmetry breaking, by which small spatial differences in the underlying ...
The structure of human CRMP-4 is a valuable new addition to the library of human CRMP family structures, with CRMP-4 being the fourth of the five members to be structurally characterized. While it still does not provide a final explanation for the prevalence of hetero-oligomer over homo-oligomer formation by CRMPs, a number of important interactions at the tetramerization interfaces have been revealed. Furthermore, our results shed light on disease-associated mutations, which can now be investigated further, such as those observed in patients with the motor neuron disease ALS. Structural analysis helped to further account for the lack of DHPase-like enzymatic activity in CRMPs, in spite of the overall structural similarity between CRMPs and DHPases. At the same time, we suggest a possible explanation for the residual HDAC activity of CRMP-3 based on a homology model calculated in the present study. However, future structural studies of the CRMP family, especially the structures of ...
All we need from you is a couple of sentences/bullet points for this gene describing 1) how the protein functions, 2) what pathway it is in (if relevant) and 3) what are its main biological roles, preferably using terms suitable for a general, non-Drosophilist audience. Here is an example: nervy (nvy) is a member of the MTG family of genes that have both nuclear and cytosolic functions. nvy encodes a transcriptional repressor and an A kinase anchoring protein (AKAP). It regulates repulsive axon guidance and functions in Plexin and Notch signaling pathways. For those genes currently lacking a gene snapshot, FlyBase welcomes contributions through our online form (also accessible from the snapshot field of the gene). Feedback on existing Gene Snapshots can be made by clicking on the Contact FlyBase link (also accessible from the bottom of every FlyBase page) and selecting the Gene Snapshots option. ...
The IUPHAR/BPS Guide to Pharmacology. semaphorin 4D (CD100) - CD molecules. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
The vascular and nervous systems are organized with well defined and accurate networks, which represent the anatomical structure enabling their functions. In recent years, it has been clearly demonstrated that these two systems share in common several mechanisms and specificities. For instance, the networking properties of the nervous and vascular systems are governed by common cues that in the brain regulate axon connections and in the vasculature remodel the primitive plexus towards the vascular tree. Here, we summarize the role of semaphorins as a paradigmatic example of the role of axon guidance molecules in physiological and pathological angiogenesis. Finally, we discuss the presence in blood vessels of neurexin and neuroligin, two proteins that finely modulate synaptic activity in the brain. This observation is suggestive of an intriguing new class of molecular and functional parallels between neurons and vascular cells.
Oral cancer is common among men in the developed world and among the most difficult neoplasms to treat. The growth and metastasis of all solid tumors requires i...
Tyrosine, Phosphorylation, Brain, Kinases, Mass Spectrometry, Spectrometry, Proteins, Kinase, Family, Growth, Migration, Clustering, Identification, Sh2 Domains, Brains, Collapsin, Genes, Growth Cone, Isoforms, Mice
How to understand some of the possible causes for dog collapse or weakness and what may be done to help prevent or deal with the problem.