Rab5a

Summary

Gene Symbol: Rab5a
Description: RAB5A, member RAS oncogene family
Alias: ras-related protein Rab-5A, small GTP-binding protein rab5
Species: rat
Products:     Rab5a

Top Publications

  1. De Hoop M, Huber L, Stenmark H, Williamson E, Zerial M, Parton R, et al. The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis. Neuron. 1994;13:11-22 pubmed
    b>Rab5a is a small GTPase that regulates fusion of endocytic vesicles to early endosomes. We investigated whether Rab5a is involved in early endocytic traffic in both the axonal and the somatodendritic domains of polarized neurons...
  2. Blümer J, Rey J, Dehmelt L, Mazel T, Wu Y, Bastiaens P, et al. RabGEFs are a major determinant for specific Rab membrane targeting. J Cell Biol. 2013;200:287-300 pubmed publisher
    ..minimal targeting machinery for recruiting Rabs from the cytosol to the correct membrane using the Rab-GEF pairs Rab5A-Rabex-5, Rab1A-DrrA, and Rab8-Rabin8 as model systems...
  3. Ikin A, Annaert W, Takei K, De Camilli P, Jahn R, Greengard P, et al. Alzheimer amyloid protein precursor is localized in nerve terminal preparations to Rab5-containing vesicular organelles distinct from those implicated in the synaptic vesicle pathway. J Biol Chem. 1996;271:31783-6 pubmed
    ..Thus, it appears that nerve terminal APP is contained predominantly in large vesicular organelles, distinct from synaptic vesicles and from the synaptic vesicle recycling pathway. ..
  4. Liu J, Lamb D, Chou M, Liu Y, Li G. Nerve growth factor-mediated neurite outgrowth via regulation of Rab5. Mol Biol Cell. 2007;18:1375-84 pubmed
    ..Thus, NGF signaling down-regulates Rab5 activity via RabGAP5 to facilitate neurite outgrowth and differentiation. ..
  5. Schindler C, Chen Y, Pu J, Guo X, Bonifacino J. EARP is a multisubunit tethering complex involved in endocytic recycling. Nat Cell Biol. 2015;17:639-50 pubmed publisher
    ..Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. These findings implicate EARP in canonical membrane-fusion events in the process of endocytic recycling. ..
  6. Gerondopoulos A, Bastos R, Yoshimura S, Anderson R, Carpanini S, Aligianis I, et al. Rab18 and a Rab18 GEF complex are required for normal ER structure. J Cell Biol. 2014;205:707-20 pubmed publisher
    ..Micro syndrome is therefore a disease characterized by direct loss of Rab18 function or loss of Rab18 activation at the ER by its GEF Rab3GAP. ..
  7. Guo X, Farías G, Mattera R, Bonifacino J. Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon. Proc Natl Acad Sci U S A. 2016;113:E5318-27 pubmed publisher
    ..These findings emphasize the importance of both biosynthetic sorting and axonal retrieval for the polarized distribution of somatodendritic receptors at steady state. ..
  8. Watson R, Pessin J. GLUT4 translocation: the last 200 nanometers. Cell Signal. 2007;19:2209-17 pubmed
    ..Future work will focus on identifying the key insulin targets that regulate the GLUT4 docking/fusion processes. ..
  9. Su X, Lodhi I, Saltiel A, Stahl P. Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5. J Biol Chem. 2006;281:27982-90 pubmed
    ..The small GTPase Rab5 is a key regulator of endocytosis. Three Rab5 isoforms (Rab5a, -5b, and -5c) have been identified...

More Information

Publications53

  1. Kanaani J, Diacovo M, El Husseini A, Bredt D, Baekkeskov S. Palmitoylation controls trafficking of GAD65 from Golgi membranes to axon-specific endosomes and a Rab5a-dependent pathway to presynaptic clusters. J Cell Sci. 2004;117:2001-13 pubmed
    ..Here, we show that palmitoylated GAD65 colocalizes with the small GTP-binding protein Rab5a in Golgi membranes and in axons but not in dendrites...
  2. Zhong P, Liu W, Gu Z, Yan Z. Serotonin facilitates long-term depression induction in prefrontal cortex via p38 MAPK/Rab5-mediated enhancement of AMPA receptor internalization. J Physiol. 2008;586:4465-79 pubmed publisher
    ..It provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes that are mediated by synaptic plasticity in PFC neurons. ..
  3. Bucci C, Wandinger Ness A, Lutcke A, Chiariello M, Bruni C, Zerial M. Rab5a is a common component of the apical and basolateral endocytic machinery in polarized epithelial cells. Proc Natl Acad Sci U S A. 1994;91:5061-5 pubmed
    In nonpolarized cells, the small GTPase Rab5a is localized to the plasma membrane, clathrin-coated vesicles, and early endosomes...
  4. Wilson J, de Hoop M, Zorzi N, Toh B, Dotti C, Parton R. EEA1, a tethering protein of the early sorting endosome, shows a polarized distribution in hippocampal neurons, epithelial cells, and fibroblasts. Mol Biol Cell. 2000;11:2657-71 pubmed
    ..EEA1 could provide specificity and directionality to fusion events occurring in a subset of these endosomes in polarized and nonpolarized cells. ..
  5. Pavlos N, Gr Nborg M, Riedel D, Chua J, Boyken J, Kloepper T, et al. Quantitative analysis of synaptic vesicle Rabs uncovers distinct yet overlapping roles for Rab3a and Rab27b in Ca2+-triggered exocytosis. J Neurosci. 2010;30:13441-53 pubmed publisher
    ..fluorescence microscopy, we have determined the exocytotic (Rab3a, Rab3b, Rab3c, and Rab27b) and endocytic (Rab4b, Rab5a/b, Rab10, Rab11b, and Rab14) Rab machinery of SVs...
  6. Yamamoto H, Komekado H, Kikuchi A. Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev Cell. 2006;11:213-23 pubmed
    ..Thus, caveolin plays critical roles in inducing the internalization of LRP6 and activating the Wnt/beta-catenin pathway. We also discuss the idea that distinct endocytic pathways correlate with the specificity of Wnt signaling events. ..
  7. Nashida T, Yoshie S, Imai A, Shimomura H. Co-localization of rab4 with endocytosis-related proteins in the rat parotid glands. Arch Histol Cytol. 2003;66:45-52 pubmed
    ..Actin, alpha-adaptin, Rab5A and aquaporin5 were detected in the Rab4-containing intracellular membrane fraction prepared using anti-Rab4 ..
  8. Marchand S, Devillers Thiery A, Pons S, Changeux J, Cartaud J. Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts. J Neurosci. 2002;22:8891-901 pubmed
    ..These data also raise the interesting hypothesis of the participation of the raft machinery in the targeting of signaling molecules to synaptic sites. ..
  9. Yuasa K, Yamagami S, Nagahama M, Tsuji A. Trafficking of cGMP-dependent protein kinase II via interaction with Rab11. Biochem Biophys Res Commun. 2008;374:522-6 pubmed publisher
    ..These data indicate that Rab11b is necessary for the trafficking of cGK-II and that the cGMP/cGK-II signaling pathway is closely related to Rab11b recycling pathway. ..
  10. Qin Y, Deng Y, Ricketts C, Srikantan S, Wang E, Maher E, et al. The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function. Hum Mol Genet. 2014;23:2428-39 pubmed publisher
    ..Our data map the tumor-suppressive properties of TMEM127 to modulation of mTOR function in the endolysosome, a feature that may contribute to both pheochromocytoma and RCC pathogenesis. ..
  11. Mehrpour M, Esclatine A, Beau I, Codogno P. Overview of macroautophagy regulation in mammalian cells. Cell Res. 2010;20:748-62 pubmed publisher
  12. Lee S, Kim A, Kim J, Kim J, Lee J, Lee Y, et al. The proteins of synaptic vesicle membranes are affected during ageing of rat brain. Exp Mol Med. 2001;33:220-5 pubmed
    ..and 20 months old rat brain respectively showed no difference in the level of Rab family proteins (Rab3A and Rab5A). However, Rho family proteins such as RhoA and Cdc42 were elevated in LP2 membranes of the aged brain...
  13. Woller B, Luiskandl S, Popovic M, Prieler B, Ikonge G, Mutzl M, et al. Rin-like, a novel regulator of endocytosis, acts as guanine nucleotide exchange factor for Rab5a and Rab22. Biochim Biophys Acta. 2011;1813:1198-210 pubmed publisher
    RIN proteins serve as guanine nucleotide exchange factors for Rab5a. They are characterized by the presence of a RIN homology domain and a C-terminal Vps9 domain. Currently three family members have been described and analyzed...
  14. Star E, Newton A, Murthy V. Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function. J Physiol. 2005;569:103-17 pubmed
    We investigated the roles of two Rab-family proteins, Rab3a and Rab5a, in hippocampal synaptic transmission using real-time fluorescence imaging...
  15. Zhao Z, Sagare A, Ma Q, Halliday M, Kong P, Kisler K, et al. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance. Nat Neurosci. 2015;18:978-87 pubmed publisher
    ..Thus, PICALM regulates Aβ BBB transcytosis and clearance, which has implications for Aβ brain homeostasis and clearance therapy. ..
  16. Pons V, Luyet P, Morel E, Abrami L, van der Goot F, Parton R, et al. Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. PLoS Biol. 2008;6:e214 pubmed publisher
    ..PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis. ..
  17. Liu L, He B, Liu W, Zhou D, Cox J, Zhang X. Tetraspanin CD151 promotes cell migration by regulating integrin trafficking. J Biol Chem. 2007;282:31631-42 pubmed
    ..In conclusion, the YXXvarphi motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins. ..
  18. Oku S, Takahashi N, Fukata Y, Fukata M. In silico screening for palmitoyl substrates reveals a role for DHHC1/3/10 (zDHHC1/3/11)-mediated neurochondrin palmitoylation in its targeting to Rab5-positive endosomes. J Biol Chem. 2013;288:19816-29 pubmed publisher
  19. Nechiporuk T, Fernandez T, Vasioukhin V. Failure of epithelial tube maintenance causes hydrocephalus and renal cysts in Dlg5-/- mice. Dev Cell. 2007;13:338-50 pubmed
    ..These findings show that Dlg5 is causally involved in hydrocephalus and renal cysts and reveal that targeted membrane delivery of cadherin-catenin adhesion complexes is critical for cell polarity and epithelial tube maintenance. ..
  20. Takamori S, Holt M, Stenius K, Lemke E, Gr Nborg M, Riedel D, et al. Molecular anatomy of a trafficking organelle. Cell. 2006;127:831-46 pubmed publisher
  21. Gruenheid S, Pinner E, Desjardins M, Gros P. Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med. 1997;185:717-30 pubmed
  22. Huang C, You J, Wu M, Hsu K. Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI.Rab5 complex. Potential role in (S)-3,5-dihydroxyphenylglycene-induced long term depression. J Biol Chem. 2004;279:12286-92 pubmed
    ..These results suggest an important role for Rap1-MKK3/6-p38 MAPK pathway in the induction of mGluR-dependent LTD by directly coupling to receptor trafficking machineries to facilitate the loss of synaptic AMPA receptors. ..
  23. Kaddai V, Le Marchand Brustel Y, Cormont M. Rab proteins in endocytosis and Glut4 trafficking. Acta Physiol (Oxf). 2008;192:75-88 pubmed publisher
  24. Mamo A, Jules F, Dumaresq Doiron K, Costantino S, Lefrancois S. The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. Mol Cell Biol. 2012;32:1855-66 pubmed publisher
    ..Taken together, our results support a role for CLN5 in controlling the itinerary of the lysosomal sorting receptors by regulating retromer recruitment at the endosome. ..
  25. Wolff N, Lee W, Abouhamed M, Thevenod F. Role of ARF6 in internalization of metal-binding proteins, metallothionein and transferrin, and cadmium-metallothionein toxicity in kidney proximal tubule cells. Toxicol Appl Pharmacol. 2008;230:78-85 pubmed publisher
    ..endogenous ARF6 was associated with the plasma membrane (PM) as well as juxtanuclear and co-localized with Rab5a and Rab11 involved in early and recycling endosomal trafficking...
  26. Sirokmány G, Szidonya L, Káldi K, Gaborik Z, Ligeti E, Geiszt M. Sec14 homology domain targets p50RhoGAP to endosomes and provides a link between Rab and Rho GTPases. J Biol Chem. 2006;281:6096-105 pubmed
    ..We suggest that p50RhoGAP provides a link between Rab and Rho GTPases in the regulation of receptor-mediated endocytosis. ..
  27. Wu K, He M, Hou Q, Sheng A, Yuan L, Liu F, et al. Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections. Sci Signal. 2014;7:ra81 pubmed publisher
    ..Thus, our findings suggest that Rab5, its effector Rabaptin-5, and its regulator Rabex-5 mediate Sema3A-induced axon guidance during brain development. ..
  28. Roosterman D, Cottrell G, Schmidlin F, Steinhoff M, Bunnett N. Recycling and resensitization of the neurokinin 1 receptor. Influence of agonist concentration and Rab GTPases. J Biol Chem. 2004;279:30670-9 pubmed
    ..High SP (10 nM) induced translocation of the NK1R and beta-arrestin 1 to perinuclear sorting endosomes containing Rab5a, where NK1R remained for >60 min...
  29. Verges M, Havel R, Mostov K. A tubular endosomal fraction from rat liver: biochemical evidence of receptor sorting by default. Proc Natl Acad Sci U S A. 1999;96:10146-51 pubmed
  30. Chen C, Garcia Santos D, Ishikawa Y, Seguin A, Li L, Fegan K, et al. Snx3 regulates recycling of the transferrin receptor and iron assimilation. Cell Metab. 2013;17:343-52 pubmed publisher
    ..Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism. ..
  31. Brown T, Tran I, Backos D, Esteban J. NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron. 2005;45:81-94 pubmed
    ..We propose a model in which synaptic activity leads to Rab5 activation, which in turn drives the removal of AMPA receptors from synapses. ..
  32. Ma Z, Wang H, Wu L, Zhui L, Shi W, Ma D, et al. RNAi-mediated Rab5a suppression inhibits proliferation and migration of vascular smooth muscle cells. Acta Cardiol. 2010;65:507-14 pubmed
    ..We tested the hypothesis that down-regulation of Rab5a, a prototypical member of the Rab family of GTPases, leads to inhibition ofVSMC proliferation and migration in the ..
  33. Zhu G, Zhai P, Liu J, Terzyan S, Li G, Zhang X. Structural basis of Rab5-Rabaptin5 interaction in endocytosis. Nat Struct Mol Biol. 2004;11:975-83 pubmed
    ..Biochemical and functional analyses show that the crystallographically observed Rab5-Rabaptin5 complex also exists in solution, and disruption of this complex by mutation abrogates endosome fusion. ..
  34. Nakatsu F, Messa M, Nández R, Czapla H, Zou Y, Strittmatter S, et al. Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway. J Cell Biol. 2015;209:85-95 pubmed publisher
    ..Sac2/INPP5F and OCRL may cooperate in the sequential dephosphorylation of PI(4,5)P2 at the 5 and 4 position of inositol in a partnership that mimics that of the two phosphatase modules of synaptojanin. ..
  35. Potokar M, Lacovich V, Chowdhury H, Kreft M, Zorec R. Rab4 and Rab5 GTPase are required for directional mobility of endocytic vesicles in astrocytes. Glia. 2012;60:594-604 pubmed publisher
  36. Sedej S, Rupnik M, Zorec R. Endocytosis-dominated membrane area decrease requires Rab5 protein in rat melanotrophs. Ann N Y Acad Sci. 2005;1048:272-80 pubmed
    ..At high [Ca(2+)](i), Rab5 antibody did not affect the steady-state increase in membrane capacitance, while it elevated the rate of membrane capacitance increase, which is consistent with an inhibition of endocytosis. ..
  37. Hagiwara M, Shirai Y, Nomura R, Sasaki M, Kobayashi K, Tadokoro T, et al. Caveolin-1 activates Rab5 and enhances endocytosis through direct interaction. Biochem Biophys Res Commun. 2009;378:73-8 pubmed publisher
    ..The results showed that overexpression of the Rab5 binding domain of caveolin-1 increase the amount of Rab5-GTP in Cos-1 cells. These findings imply that caveolin-1 controls the Rab5 activity during the caveolae-mediated endocytosis. ..
  38. Schaheen B, Dang H, Fares H. Derlin-dependent accumulation of integral membrane proteins at cell surfaces. J Cell Sci. 2009;122:2228-39 pubmed publisher
  39. Berger K, Cooper J, Heaton N, Yoon R, Oakland T, Jordan T, et al. Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009;106:7577-82 pubmed publisher
    ..We identified 7 host cofactors of viral replication, including Cdc42 and Rock2 (actin polymerization), EEA1 and Rab5A (early endosomes), Rab7L1, and PI3-kinase C2gamma and PI4-kinase IIIalpha (phospholipid metabolism)...
  40. Hyvola N, Diao A, McKenzie E, Skippen A, Cockcroft S, Lowe M. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. EMBO J. 2006;25:3750-61 pubmed
    ..We conclude that rabs play a dual role in regulation of OCRL1, firstly targeting it to the Golgi apparatus and endosomes, and secondly, directly stimulating the 5-phosphatase activity of OCRL1 after membrane recruitment. ..
  41. Gauthier Campbell C, Bredt D, Murphy T, El Husseini A. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004;15:2205-17 pubmed
    ..These results demonstrate that select dually lipidated protein motifs trigger changes in the development and growth of neuronal processes. ..
  42. Wagner A, Strowski M, Williams J. Identification of Rab 5 but not Rab 3A in rat pancreatic zymogen granule membranes. Biochem Biophys Res Commun. 1994;200:542-8 pubmed
    ..Of these, Rab 5 was identified in purified zymogen granule membranes where it may be involved in the endocytotic retrieval of granule membrane following exocytosis. ..
  43. Ostrowski M, Carmo N, Krumeich S, Fanget I, Raposo G, Savina A, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19-30; sup pp 1-13 pubmed publisher
    ..Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo. ..
  44. Sun P, Yamamoto H, Suetsugu S, Miki H, Takenawa T, Endo T. Small GTPase Rah/Rab34 is associated with membrane ruffles and macropinosomes and promotes macropinosome formation. J Biol Chem. 2003;278:4063-71 pubmed
    ..These results imply that Rah is required for efficient macropinosome formation from the membrane ruffles. ..