In the present study, we demonstrated that clathrin and AP-1 are required for the retrograde transport from recycling endosomes to the Golgi. CTxB appeared to reach recycling endosomes in the clathrin- or AP-1-knockdown cells, similar to in control cells, suggesting that clathrin and AP-1 are not essential for the transport of CTxB from the plasma membrane through early endosomes to recycling endosomes. It has been shown that clathrin localizes to the TGN, early endosomes and the plasma membrane (Brodsky, 2012). We showed that CHC also localized to recycling endosomes. CHC colocalized with the recycling endosome proteins, Rab11, Tfn and SMAP2 in COS-1 cells (in which the Golgi, early endosomes and recycling endosomes are spatially distinct) (Lee et al., 2015; Misaki et al., 2007; Uchida et al., 2011). The recycling endosomes that were dispersed from the perinuclear region to the cytoplasm by nocodazole treatment remained positive for CHC. The localization of AP-1 to recycling endosomes (Folsch ...
Regardless of the type of endocytosis, vesicles are fused with an internal membranous compartment known as endosome. Intramecellular compartments formed after phagocytosis and macropinocytosis beccome particular types of endosomes known as phagosome and macropinosome, respectively. Endosomes show an irregular shape, like large bags, although sometimes they form tubular structures. Like the TGN of the Golgi complex , endosomes are stations for receiving and distributing molecules packed in vesicles. Vesicles arrive to endosomes from the plasma membrane and from the TGN of the Golgi complex. From endosomes, vesicles leave toward the plasma membrane or TGN of the Golgi complex, both are pathways for recycling membrane receptors and lipids. However, most of the molecules in the endosomes are transported to lysosomes for degradation. Two ways of endosomal organization have been proposed: a) Cells would contain several types of endosomes. Early endosomes close to the plasma membrane that receive ...
In cell biology, an endosome is a membrane-bounded compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature. Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL ...
P-selectin is not sorted from LDL receptor in late endosomes. P-selectin is transported to the TGN approximately eight to nine times faster than it is delivered to lysosomes in PC12 cells (20-25 min vs. 3-3.8 h), showing that P-selectin molecules entering late endosomes are eight to nine times more likely to recycle to the TGN than to go directly to lysosomes. The ratio of these two transport rates is similar for LDL receptor (t1/2 = 2-2.5 h to the TGN vs. 20 h to lysosomes; Green and Kelly 1992). The simplest explanation for these observations is that both proteins have the same sorting phenotype in late endosomes (Fig. 1A and Fig. B). Therefore, the short half-life of P-selectin is most likely not due to its selective targeting to lysosomes, as has been suggested (Blagoveshchenskaya et al. 1998), but is due to its selective delivery from sorting endosomes to late endosomes. One significant consequence of this sorting event is rapid recycling of P-selectin through the TGN. Rapid turnover of ...
The endocytic pathway is essential for cell homeostasis and numerous small GTPase Rab have been involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis, or adaptative immunity. Here we show that Rab4b is required for early endosome sorting of transferrin receptors (TfR) to the recycling endosomes and we identified the AP1γ subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosomes sorting. We show that internalized transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in absence of Rab4b while it is rapidly recycled back to the plasma membrane. On the contrary, Rab4b overexpression leads to the accumulation of internalized Tf within AP-1 and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except TfR and require AP1γ for their formation. Furthermore, ...
Enveloped viruses fuse with host membranes without affecting cell integrity. Non-enveloped viruses and bacteria penetrate by rupturing endosomal membranes and thus expose complex-type carbohydrates from the endosome lumen to cytosolic proteins. Here we report on the dynamics and initial marker analyses of Galectin-3 (Gal3)-positive membranes triggered by incoming adenovirus species B/C in HeLa cells. Using mCherry-Gal3 reporter constructs, immunolabeling, confocal and electron microscopy, we detected robust signals from Gal3-containing, early endosomal antigen 1-positive membranes 1 h post-infection (pi). Adenoviruses penetrate from non-acidic endosomes with high efficiency, 15 min pi, and largely outnumbered the Gal3-positive membranes, suggesting that Gal3 recruitment to broken membranes is transient, or Gal3-positive membranes are rapidly turned-over. In support of rapid turn-over, Gal3 was found within single-membrane vesicles and degradative autophagosomes. The Gal3 membranes contained ubiquitin
Homotypic fusion between early endosomes requires the phosphatidylinositol 3-phosphate (PI3P)-binding protein, Early Endosomal Autoantigen 1 (EEA1). We have investigated the role of other proteins that interact with EEA1 in the fusion of early endosomes derived from Baby Hamster Kidney (BHK) cells. We confirm a requirement for syntaxin 13, but additionally show that the assay is equally sensitive to reagents specifically targeted against syntaxin 6. Binding of EEA1 to immobilised GST-syntaxin 6 and 13 was directly compared; only syntaxin 6 formed a stable complex with EEA1. Early endosome fusion requires the release of intravesicular calcium, and calmodulin plays a vital role in the fusion pathway, as judged by sensitivity to antagonists. We demonstrate that both EEA1 and syntaxin 13 interact with calmodulin. In the case of EEA1, binding to calmodulin requires an IQ domain, which is adjacent to a C-terminal FYVE domain that specifically binds to PI3P. We have assessed the influence of protein binding
Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLC beta/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of ...
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for recruitment of VPS33A to the HOPS complex (PubMed:23901104). Required for fusion of endosomes and autophagosomes with lysosomes; the
Influenza viruses enter the cell inside an endosome. During the endosomal journey, acidification triggers a conformational change of the virus spike protein hemagglutinin (HA) that results in escape of the viral genome from the endosome into the cytoplasm. It is still unclear how the interplay between acidification and HA conformation changes affects the kinetics of the viral endosomal escape. We develop here a stochastic model to estimate the change of conformation of HAs inside the endosome nanodomain. Using a Markov process, we model the arrival of protons to HA binding sites and compute the kinetics of their accumulation. We compute the Mean First Passage Time (MFPT) of the number of HA bound sites to a threshold, which is used to estimate the HA activation rate for a given pH (i.e. proton concentration). The present analysis reveals that HA proton binding sites possess a high chemical barrier, ensuring a stability of the spike protein at sub -acidic pH. We predict that activating more than ...
CD63 (Late Endosomes Marker) Antibody - With BSA and Azide, Purified Mouse Monoclonal Antibody validated in WB, IHC, IF, FC, IP, E (AH10281-20), Abgent
Probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, may act as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation. May be involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking. Alternatively, may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. May indirectly play a role in neurite outgrowth.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Membranes are vital barriers by which cells control the flux of molecules and energy between their exterior and interior and also between their various intracellular compartments. While numerous transport systems exist for ions and small molecules, the cytosolic uptake of larger biological molecules and in particular antibody-targeted drugs, is a big challenge. Inducing leakage of the plasma membrane is unfavorable since the target cell specificity mediated by the antibody would likely be lost in this case. After binding and internalization, the antibody drug conjugates reach the endosomes. Thus, enforcing the endosomal escape of anti-tumor toxins without affecting the integrity of other cellular membranes is of paramount importance. Different strategies have been developed in the last decades to overcome endosomal accumulation and subsequent lysosomal degradation of targeted protein-based drugs. In this review we summarize the various efforts made to establish efficient techniques to disrupt the
In this study, we uncover a novel molecular player important for axon branching and compartmentalization. We demonstrate that Clstn-1 is critical for growth and branching of peripheral sensory axons and differentially affects the behavior of separate axons from one neuron. Furthermore, our data indicate that Clstn-1 acts in part through a trafficking role and controls the transport of endosomal carriers. Our ability to image live endosome dynamics as vertebrate neurons develop complex axon arborizations in vivo has revealed new insight into Clstn-1 function and into differential endosome dynamics in specific axon compartments. Our results suggest that regulated trafficking of early endosomes from the cell body to specific axon locations is crucial for neuronal compartmentalization and axon branching.. Precise control over axon branching is essential for neuronal circuit formation. Many factors have been shown to influence axon branching, including extracellular cues, intracellular signaling ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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MAJOR ISSUES The reviewers were not fully convinced by the endosome acidification results. Both wanted a more thorough characterization of endosome distribution and transferrin colocalization in the transferrin experiments and felt that more detail - in particular, relative to the calculation of the n values - were needed to judge the robustness of the pH experiments. 1. RE: N values and figures chosen: The authors must specify how many cells, how many different cultures from how many different animals were used for the determinations of transferrin (Fig 3) and for the assays of endosome acidification (Fig 4). Both reviewers felt that the number of endosomes tested was relatively small. These n values should be increased. Response: To address this question, we developed a method using a high-throughput confocal fluorescence imaging system, the Opera Phenix High Content Screening System, which allowed us to image and analyze thousands of cells and endosomes. Based on use of this new method and ...
Seroussi, E., Kedra, D., Kost-Alimova, M., Sandberg-Nordqvist, A., Fransson, I., Jacobs, J., ... Dumanski, J. (1999). TOM1 Genes Map to Human Chromosome 22q13.1 and Mouse Chromosome 8C1 and Encode Proteins Similar to the Endosomal Proteins HGS and STAM. Genomics, 57, 380 - 388 ...
J Immunol. 2008 Jun 15;180(12):8192-203. Platelet-activating factor-mediated endosome formation causes membrane translocation of p67phox and p40phox that requires recruitment and activation of p38 MAPK, Rab5a, and phosphatidylinositol 3-kinase in human neutrophils. McLaughlin NJ, Banerjee A, Khan SY, Lieber JL, Kelher MR, Gamboni-Robertson F, Sheppard FR, Moore EE, Mierau GW, Elzi DJ, Silliman CC ...
The total amount of p-EGFR in endosomes decays with the same kinetics asthe number of endosomes with p-EGFR.Time course of total integral p-EGFR intensity in en
Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN ...
The collection of specimens illustrated in this section demonstrates the effectiveness of the Nikon YFP HYQ filter combination with a series of cell lines containing a chimeric EYFP plasmid vector that expresses a fluorescent fusion protein targeted at the cellular endosomal network.
This elegant study identifies Arc as a presenilin-1 (PS1) interacting protein that links synaptic activity with γ-secretase processing of APP in neurons. Detailed analysis of subcellular localization of APP, PS1, and Arc by immunofluorescence and immunoelectron microscopy methods suggest a mechanism whereby Arc facilitates association of PS1 with endosomes that contain internalized APP. Thus, it appears that the subset of APP that contributes to activity-dependent Aβ production encounters PS1 in endocytic organelles in dendrites of excitatory neurons.. Arc is known to associate with endophilin-2/3 and dynamin on endosomes, and mediate AMPA receptor (AMPAR) endocytosis. Whereas the last is markedly reduced in Arc knockout neurons, this does not appear to be the case with PS1 or APP. Whether this indicates Arc regulation of PS1/APP colocalization in tubulovesicular endosomes is distinct from its function in regulating the endocytic machinery responsible for AMPAR endocytosis remains to be ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec-1 domain family, and it encodes a protein similar to the yeast class C Vps33 protein. The mammalian class C VPS proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. [provided by RefSeq, Jul 2008 ...
マウス・モノクローナル抗体 ab70521 交差種: Hu 適用: ICC/IF…EEA1抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
Are you suggesting that the protein is being endocytosed rather than expressed in the cultured primary cells? I doubt that would be the case because on fusion of the endosome with a lysosome the proteins in the vesicle are usually degraded by the lysosomal enzymes. For the protein to enter using endosomes, it would have to either resist proteolytic degradation or prevent fusion of the endosome and lysosome. Further, the protein would have to escape from the endosome if it is to function in the cytosol. It may not be impossible for an intact protein to both survive and escape from the endocytotic pathway, but it is not common ...
Endosomal networks in immunology When a T cell in our immune system gets the right signal it leaps into action within seconds - taking on one of many different roles in fighting the infection. Jérémie Rossy and his group are using single molecule imaging to examine how messages received at the cell surface are transmitted via the membrane and specialised compartments within the cell, such as endosomes.
Polyclonal antibody for SR D1/CD68 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Mouse. SR D1/CD68 information: Molecular Weight: 34818 MW; Subcellular Localization: Isoform Long: Endosome membrane; Single-pass ty
EEA1 antibody [C3], C-term (early endosome antigen 1) for ICC/IF, IHC-P, WB. Anti-EEA1 pAb (GTX109638) is tested in Human, Mouse, Rat, Hamster samples. 100% Ab-Assurance.
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ROBLD3, 0.1 mg. The late endosomal/lysosomal adaptor MAPK and MTOR activator 2 (LAMTOR2) protein belongs to the LAMTOR family of proteins, and together with LAMTOR3 and the MAPK1 and ERK kise 1 (MEK1) localizes to late endosomes where it is required for
The product of this gene is highly conserved with a mouse protein associated with the cytoplasmic face of late endosomes and lysosomes. The mouse…
Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a prominent substrate for activated tyrosine kinase receptors that has been proposed to play a role in endosomal membrane trafficking. The protein contains a FYVE domain, which specifically binds to the lipid phosphatidylinositol (PI) 3-phosphate (PI 3-P). We show that this interaction is required both for correct localization of the protein to endosomes that only partially coincides with early endosomal autoantigen 1 and for efficient tyrosine phosphorylation of the protein in response to epidermal growth factor stimulation. Treatment with wortmannin reveals that Hrs phosphorylation also requires PI 3-kinase activity, which is necessary to generate the PI 3-P required for localization. We have used both hypertonic media and expression of a dominant-negative form of dynamin (K44A) to inhibit endocytosis; under which conditions, receptor stimulation fails to elicit phosphorylation of Hrs. Our results provide a clear example of the
Immune responses are initiated when molecules of microbial origin are sensed by the Toll-like receptors (TLRs). We now report the identification of essential molecular components for the trafficking of the lipopolysaccharide (LPS) receptor complex. LPS was endocytosed by a receptor-mediated mechanism dependent on dynamin and clathrin and colocalized with TLR4 on early/sorting endosomes. TLR4 was ubiquitinated and associated with the ubiquitin-binding endosomal sorting protein hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs. Inhibition of endocytosis and endosomal sorting increased LPS signaling. Finally, the LPS receptor complex was sorted to late endosomes/lysosomes for degradation and loading of associated antigens onto HLA class II molecules for presentation to CD4+ T cells. Our results show that endosomal trafficking of the LPS receptor complex is essential for signal termination and LPS-associated antigen presentation, thus controlling both innate and adaptive immunity through
Phosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11- and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4(C407A), the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of
Endosomal internalisation and subsequent lysosomal degradation of membrane proteins is important for regulation of multiple cellular processes, among these the termination of receptor signalling and degradation of misfolded membrane proteins. ESCRT (Endosomal sorting complex required for transport) proteins are vital for the sorting of ubiquitinated membrane proteins into multivesicular bodies for subsequent degradation in the lysosome. In this study we generated two stable cell lines expressing the EGFP tagged ESCRT proteins Hrs and hVps22. Our goal was to utilise these cell lines for investigations into ESCRT protein dynamics, the relative order of ESCRT protein recruitment to the endosomes, and the endosomal localisation of ESCRT proteins. However, though the EGFP-Hrs cell line seemed to express a functional Hrs protein, the EGFP-hVps22 protein was completely cytosolic and could not be visualised on endosomes. hVps4, and its mouse homologue Skd1 is an AAA-type ATPase shown to be necessary for ...
It is well established that dynamin is involved in clathrin-dependent endocytosis, but relatively little is known about possible intracellular functions of this GTPase. Using confocal imaging, we found that endogenous dynamin was associated with the plasma membrane, the trans-Golgi network, and a perinuclear cluster of cation-independent mannose 6-phosphate receptor (CI-MPR)-containing structures. By electron microscopy (EM), it was shown that these structures were late endosomes and that the endogenous dynamin was preferentially localized to tubulo-vesicular appendices on these late endosomes. Upon induction of the dominant-negative dynK44A mutant, confocal microscopy demonstrated a redistribution of the CI-MPR in mutant-expressing cells. Quantitative EM analysis of the ratio of CI-MPR to lysosome-associated membrane protein-1 in endosome profiles revealed a higher colocalization of the two markers in dynK44A-expressing cells than in control cells. Western blot analysis showed that ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
We identified p18 as a potential component of lipid rafts. The predominant distribution of p18 to DRMs suggested its potential localization to lipid rafts. However, it is currently accepted that DRMs do not necessarily correspond to lipid rafts and that the DRM separation method is insufficient for the identification of lipid raft‐associated proteins (Lichtenberg et al, 2005; Hancock, 2006). Thus, to verify the raft localization of p18, we examined intracellular distribution of p18 and its mutants. The cell staining analyses showed that p18 could be colocalized with GM1 ganglioside, a marker of lipid rafts (Harder et al, 1998), and that the N‐terminal potential myristoylation and palmitoylation sites, which are known to function as lipid raft localization signals, were required for the late endosome localization of p18. These observations strongly supported the presence of p18 in lipid rafts of late endosomes (Balbis et al, 2007). It is of interest that the N‐terminal only 20 residues of ...
Looking for online definition of sorting endosome in the Medical Dictionary? sorting endosome explanation free. What is sorting endosome? Meaning of sorting endosome medical term. What does sorting endosome mean?
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TY - JOUR. T1 - Brefeldin A rapidly disrupts plasma membrane polarity by blocking polar sorting in common endosomes of MDCK cells. AU - Wang, E.. AU - Pennington, J. G.. AU - Goldenring, J. R.. AU - Hunziker, W.. AU - Dunn, Kenneth. PY - 2001. Y1 - 2001. N2 - Recent studies showing thorough intermixing of apical and basolateral endosomes have demonstrated that endocytic sorting is critical to maintaining the plasma membrane polarity of epithelial cells. Our studies of living, polarized cells show that disrupting endocytosis with brefeldin-A rapidly destroys the polarity of transferrin receptors in MDCK cells while having no effect on tight junctions. Brefeldin-A treatment induces tubulation of endosomes, but the sequential compartments and transport steps of the transcytotic pathway remain intact. Transferrin is sorted from LDL, but is then missorted from common endosomes to the apical recycling endosome, as identified by its nearly neutral pH, and association with GFP chimeras of Rabs 11a and ...
Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease ...
CHMP2B Full-Length MS Protein Standard (NP_054762), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration.
The retromer is a phylogenetically conserved multisubunit complex that mediates retrograde transport of transmembrane cargo from endosomes to the TGN (Seaman, 2005; Bonifacino and Rojas, 2006; Bonifacino and Hurley, 2008). The best-characterized cargo for the mammalian retromer is the cation-independent mannose 6-phosphate receptor (MPR [CI-MPR]), one of two intracellular sorting receptors that participates in the delivery of acid hydrolases to lysosomes (Kornfeld, 1992). The CI-MPR binds newly synthesized acid hydrolases at the TGN and carries them within clathrin-coated vesicles to endosomes, where the hydrolases are released for eventual transport to lysosomes. The retromer functions to retrieve the unoccupied receptors to the TGN, where they engage in further cycles of acid hydrolase sorting. Depletion of retromer subunits by RNAi prevents this retrieval, leading to rerouting of the receptors to lysosomes and consequent leakage of newly synthesized acid hydrolases into the extracellular ...
This is calculation with bound lipids. Acyl chains of two lipids were modelled. Calculated hydrocarbon boundary of the lipid bilayer corresponds to the carbonyl groups of the bound lipid. Depending on conformations of bound lipids, the protein can penetrate deeper by ~2 A. Results for the dimer without bound lipids are exactly the same as for lipid-free EEA1 monomer (1hyi). Transfer energy was calculated without contribution from the bound lipid ...
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinsons disease (PD), and variants increase the risk for sporadic PD. LRRK2 displays kinase and GTPase activity, and altered catalytic activity correlates with neurotoxicity, making LRRK2 a promising therapeutic target. Despite the importance of LRRK2 for disease pathogenesis, its normal cellular function, and the mechanism(s) by which pathogenic mutations cause neurodegeneration remain unclear. LRRK2 seems to regulate a variety of intracellular vesicular trafficking events to and from the late endosome in a manner dependent on various Rab proteins. At least some of those events are further regulated by LRRK2 in a manner dependent on two-pore channels (TPCs). TPCs are ionic channels localized to distinct endosomal structures and can cause localized calcium release from those acidic stores, with downstream effects on vesicular trafficking. Here, we review current knowledge about the link ...
If you have a question about this talk, please contact Mihoko Tame.. Abstract not available. This talk is part of the Developmental Biology Seminar Series series.. ...