Skip to main content

Rab7a in Endocytosis and Signaling

  • Reference work entry
Encyclopedia of Signaling Molecules

Synonyms

BRL-Ras; CMT2B; FLJ20819; PRO2706; RAB7a; Ras-related protein Rab-7a; Ypt7p (yeast ortholog)

Rab7 Historical Background and Function

Mammalian Rab7 was first identified in a rat liver cell line as BRL-Ras [X12535; NM_023950] and subsequently named Rab7 when it was recognized to be a member of an emerging, separate branch of Ras-related GTPases now well known as the Rab family of GTPases [NP_004628.4; P51149; P09527]. Rab7a is the most widely studied form and encoded on human chromosome 3q21.3 (mouse chromosome 6) as two splice variants differing in the 3′ untranslated region. The most intensively studied mammalian forms of Rab7a (mouse, canine, rat, and human) are 99.5% identical with only a single conservative change among the 207 amino acids (D/E 196). A more recently discovered homolog, Rab7b/Rab7L1, is encoded on human and mouse chromosome 1q32 and functions in late endosome to Golgi trafficking [Q96AH8; Q8VEA8]. Human Rab7b is only 47% identical and 82% homologous to...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Agola J, Jim P, Ward H, Basuray S, Wandinger-Ness A. Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities. Clin Genet. 2011;80:305–18.

    Article  CAS  Google Scholar 

  • BasuRay S, Mukherjee S, Romero E, Wilson MC, Wandinger-Ness A. Rab7 mutants associated with Charcot-Marie-Tooth disease exhibit enhanced NGF-stimulated signaling. PLoS One. 2010;5:e15351.

    Article  PubMed  CAS  Google Scholar 

  • Cao C, Backer JM, Laporte J, Bedrick EJ, Wandinger-Ness A. Sequential actions of myotubularin lipid phosphatases regulate endosomal PI(3)P and growth factor receptor trafficking. Mol Biol Cell. 2008;19:3334–46.

    Article  PubMed  CAS  Google Scholar 

  • Caviston JP, Zajac AL, Tokito M, Holzbaur EL. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes. Mol Biol Cell. 2011;22:478–92.

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Yang J, Low PS, Cheng JX. Cholesterol level regulates endosome motility via Rab proteins. Biophys J. 2008;94:1508–20.

    Article  PubMed  CAS  Google Scholar 

  • Cogli L, Piro F, Bucci C. Rab7 and the CMT2B disease. Biochem Soc Trans. 2009;37:1027–31.

    Article  PubMed  CAS  Google Scholar 

  • Frasa MA, Maximiano FC, Smolarczyk K, Francis RE, Betson ME, Lozano E, et al. Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation. Curr Biol. 2010;20:198–208.

    Article  PubMed  CAS  Google Scholar 

  • Geetha T, Wooten MW. TrkA receptor endolysosomal degradation is both ubiquitin and proteasome dependent. Traffic. 2008;9:1146–56.

    Article  PubMed  CAS  Google Scholar 

  • Guo A, Villen J, Kornhauser J, Lee KA, Stokes MP, Rikova K, et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci USA. 2008;105:692–7.

    Article  PubMed  CAS  Google Scholar 

  • Harbour ME, Breusegem SY, Antrobus R, Freeman C, Reid E, Seaman MN. The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010;123:3703–17.

    Article  PubMed  CAS  Google Scholar 

  • Ho CY, Alghamdi TA, Botelho RJ. Phosphatidylinositol-3,5-bisphosphate: no longer the poor PIP2. Traffic. 2012;13:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Jackson LK, Nawabi P, Hentea C, Roark EA, Haldar K. The Salmonella virulence protein SifA is a G protein antagonist. Proc Natl Acad Sci USA. 2008;105:14141–6.

    Article  PubMed  CAS  Google Scholar 

  • Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, et al. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 2008;10:776–87.

    Article  PubMed  CAS  Google Scholar 

  • Lin MG, Zhong Q. Interaction between small GTPase Rab7 and PI3KC3 links autophagy and endocytosis: a new Rab7 effector protein sheds light on membrane trafficking pathways. Small Gtpases. 2011;2:85–8.

    Article  PubMed  Google Scholar 

  • Loubery S, Wilhelm C, Hurbain I, Neveu S, Louvard D, Coudrier E. Different microtubule motors move early and late endocytic compartments. Traffic. 2008;9:492–509.

    Article  PubMed  CAS  Google Scholar 

  • Lu A, Tebar F, Alvarez-Moya B, Lopez-Alcala C, Calvo M, Enrich C, et al. A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes. J Cell Biol. 2009;184:863–79.

    Article  PubMed  CAS  Google Scholar 

  • McGough IJ, Cullen PJ. Recent advances in retromer biology. Traffic. 2011;12:963–71.

    Article  PubMed  CAS  Google Scholar 

  • Nada S, Hondo A, Kasai A, Koike M, Saito K, Uchiyama Y, et al. The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes. EMBO J. 2009;28:477–89.

    Article  PubMed  CAS  Google Scholar 

  • Peralta ER, Martin BC, Edinger AL. Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence. J Biol Chem. 2010;285:16814–21.

    Article  PubMed  CAS  Google Scholar 

  • Raiborg C, Stenmark H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature. 2009;458:445–52.

    Article  PubMed  CAS  Google Scholar 

  • Rajagopal R, Ishii S, Beebe DC. Intracellular mediators of transforming growth factor beta superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo. BMC Cell Biol. 2007;8:25.

    Article  PubMed  CAS  Google Scholar 

  • Rojas R, van Vlijmen T, Mardones GA, Prabhu Y, Rojas AL, Mohammed S, et al. Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7. J Cell Biol. 2008;183:513–26.

    Article  PubMed  CAS  Google Scholar 

  • Schroeder B, Weller SG, Chen J, Billadeau D, McNiven MA. A Dyn2-CIN85 complex mediates degradative traffic of the EGFR by regulation of late endosomal budding. EMBO J. 2010;29:3039–53.

    Article  PubMed  CAS  Google Scholar 

  • Seaman MN, Harbour ME, Tattersall D, Read E, Bright N. Membrane recruitment of the cargo-selective retromer subcomplex is catalyzed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. J Cell Sci. 2009;122:2371–82.

    Article  PubMed  CAS  Google Scholar 

  • Sun Q, Westphal W, Wong KN, Tan I, Zhong Q. Rubicon controls endosome maturation as a Rab7 effector. Proc Natl Acad Sci USA. 2010;107:19338–43.

    Article  PubMed  CAS  Google Scholar 

  • Sun Q, Zhang J, Fan W, Wong KN, Ding X, Chen S, et al. The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. J Biol Chem. 2011;286:185–91.

    Article  PubMed  CAS  Google Scholar 

  • Villen J, Beausoleil SA, Gerber SA, Gygi SP. Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci USA. 2007;104:1488–93.

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Ming Z, Xiaochun W, Hong W. Rab7: role of its protein interaction cascades in endo-lysosomal traffic. Cell Signal. 2011a;23:516–21.

    Article  PubMed  CAS  Google Scholar 

  • Wang T, Zhang M, Ma Z, Guo K, Tergaonkar V, Zeng Q, et al. A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal. J Cell Physiol. 2011b;227:2788–97.

    Google Scholar 

  • Wu YW, Tan KT, Waldmann H, Goody RS, Alexandrov K. Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators. Proc Natl Acad Sci USA. 2007;104:12294–9.

    Article  PubMed  CAS  Google Scholar 

  • Wu YW, Goody RS, Abagyan R, Alexandrov K. Structure of the disordered C terminus of Rab7 GTPase induced by binding to the Rab geranylgeranyl transferase catalytic complex reveals the mechanism of Rab prenylation. J Biol Chem. 2009;284:13185–92.

    Article  PubMed  CAS  Google Scholar 

  • Wu YW, Oesterlin LK, Tan KT, Waldmann H, Alexandrov K, Goody RS. Membrane targeting mechanism of Rab GTPases elucidated by semisynthetic protein probes. Nat Chem Biol. 2010;6:534–40.

    Article  PubMed  CAS  Google Scholar 

  • Zhang M, Chen L, Wang S, Wang T. Rab7: roles in membrane trafficking and disease. Biosci Rep. 2009;29:193–209.

    Article  PubMed  Google Scholar 

  • Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009;11:468–76.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledge PREP fellowship from NIGMS (R25GM075149) to PJ and research support from NSF (MCB0956027) to AWN and MRC (G0701444) to MNM.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soumik BasuRay .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this entry

Cite this entry

BasuRay, S., Agola, J.O., Jim, P.A., Seaman, M.N., Wandinger-Ness, A. (2012). Rab7a in Endocytosis and Signaling. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_623

Download citation

Publish with us

Policies and ethics