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Gene Review

Rab5  -  CG3664 gene product from transcript CG3664-RC

Drosophila melanogaster

Synonyms: AAF51265, BAA88244, CG3664, DRab5, Dm Rab5, ...
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Disease relevance of Rab5

  • In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions [1].

High impact information on Rab5

  • Disruption of endocytosis by dominant negative dynamin or Rab5 prevents Smo internalization [2].
  • Mutations in a second class of genes, the neoplastic tumor-suppressor genes, disrupt proteins that function either as scaffolds at cell-cell junctions (scribble, discs large, lgl) or as components of the endocytic pathway (avalanche, rab5, ESCRT components) [3].
  • Protein accumulation results from a failure in endosomal entry and progression towards lysosomal degradation; these and other avl phenotypes are also detected in Rab5 null mutant cells [4].
  • We demonstrate that the small GTPase Rab5 is required for endosome integrity in the presynaptic terminal [5].
  • Impaired Rab5 function affects endo- and exocytosis rates and decreases the evoked neurotransmitter release probability [5].

Anatomical context of Rab5

  • These enlarged endosomes are positive for Rab5 and Hrs, a protein involved in trafficking into the degradative pathway [6].
  • Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)-independent N signaling [7].
  • By contrast, GPI-AP and fluid-phase endocytosis are quantitatively unaffected at the restrictive temperature in shits hemocytes, demonstrating a constitutive dDyn and Rab5-independent endocytic pathway in Drosophila [8].
  • Analysis of mutations in beta(Heavy)-spectrin, the Drosophila brush border spectrin, reveals that this protein is necessary for the maintenance of Rab5 endosomes in the midgut [9].
  • These novel interactions between the microtubule-binding Hook1 and the large family of Rab GTPases also suggest a link between CLN3 function, microtubule cytoskeleton and endocytic membrane trafficking [10].

Associations of Rab5 with chemical compounds

  • Absence of Sprint, a receptor-recruited, Ras-activated Rab5 guanine exchange factor, gives related defects [11].

Other interactions of Rab5


  1. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Cooper, A.A., Gitler, A.D., Cashikar, A., Haynes, C.M., Hill, K.J., Bhullar, B., Liu, K., Xu, K., Strathearn, K.E., Liu, F., Cao, S., Caldwell, K.A., Caldwell, G.A., Marsischky, G., Kolodner, R.D., Labaer, J., Rochet, J.C., Bonini, N.M., Lindquist, S. Science (2006) [Pubmed]
  2. Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Zhu, A.J., Zheng, L., Suyama, K., Scott, M.P. Genes Dev. (2003) [Pubmed]
  3. Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Hariharan, I.K., Bilder, D. Annu. Rev. Genet. (2006) [Pubmed]
  4. Endocytic control of epithelial polarity and proliferation in Drosophila. Lu, H., Bilder, D. Nat. Cell Biol. (2005) [Pubmed]
  5. Role of Drosophila Rab5 during endosomal trafficking at the synapse and evoked neurotransmitter release. Wucherpfennig, T., Wilsch-Bräuninger, M., González-Gaitán, M. J. Cell Biol. (2003) [Pubmed]
  6. The conserved c2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila. Gallagher, C.M., Knoblich, J.A. Dev. Cell (2006) [Pubmed]
  7. Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling. Hori, K., Fostier, M., Ito, M., Fuwa, T.J., Go, M.J., Okano, H., Baron, M., Matsuno, K. Development (2004) [Pubmed]
  8. Shibire mutations reveal distinct dynamin-independent and -dependent endocytic pathways in primary cultures of Drosophila hemocytes. Guha, A., Sriram, V., Krishnan, K.S., Mayor, S. J. Cell. Sci. (2003) [Pubmed]
  9. Brush border spectrin is required for early endosome recycling in Drosophila. Phillips, M.D., Thomas, G.H. J. Cell. Sci. (2006) [Pubmed]
  10. Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. Luiro, K., Yliannala, K., Ahtiainen, L., Maunu, H., Järvelä, I., Kyttälä, A., Jalanko, A. Hum. Mol. Genet. (2004) [Pubmed]
  11. Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Jékely, G., Sung, H.H., Luque, C.M., Rørth, P. Dev. Cell (2005) [Pubmed]
  12. Polarized exocytosis and transcytosis of Notch during its apical localization in Drosophila epithelial cells. Sasaki, N., Sasamura, T., Ishikawa, H.O., Kanai, M., Ueda, R., Saigo, K., Matsuno, K. Genes Cells (2007) [Pubmed]
  13. Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo. Wu, S., Mehta, S.Q., Pichaud, F., Bellen, H.J., Quiocho, F.A. Nat. Struct. Mol. Biol. (2005) [Pubmed]
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