Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Rab7a in Endocytosis and Signaling

  • Soumik BasuRayEmail author
  • Jacob O. Agola
  • Patricia A. Jim
  • Matthew N. Seaman
  • Angela Wandinger-NessEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_623


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



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


  1. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Chen H, Yang J, Low PS, Cheng JX. Cholesterol level regulates endosome motility via Rab proteins. Biophys J. 2008;94:1508–20.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Cogli L, Piro F, Bucci C. Rab7 and the CMT2B disease. Biochem Soc Trans. 2009;37:1027–31.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Geetha T, Wooten MW. TrkA receptor endolysosomal degradation is both ubiquitin and proteasome dependent. Traffic. 2008;9:1146–56.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ho CY, Alghamdi TA, Botelho RJ. Phosphatidylinositol-3,5-bisphosphate: no longer the poor PIP2. Traffic. 2012;13:1–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  17. McGough IJ, Cullen PJ. Recent advances in retromer biology. Traffic. 2011;12:963–71.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Raiborg C, Stenmark H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature. 2009;458:445–52.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Villen J, Beausoleil SA, Gerber SA, Gygi SP. Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci USA. 2007;104:1488–93.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Zhang M, Chen L, Wang S, Wang T. Rab7: roles in membrane trafficking and disease. Biosci Rep. 2009;29:193–209.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pathology and Cancer Center, MSC08-4640University of New Mexico Health Sciences CenterAlbuquerqueUSA
  2. 2.Department of Clinical BiochemistryCambridge Institute for Medical ResearchCambridgeUK