Skip to main content

RAB18

  • Living reference work entry
  • First Online:
  • 68 Accesses

Synonyms

AtRabC1-C2b (Arabidopsis thaliana); Rab18b (Danio rerio); Rab-RP4 (Drosophila melanogaster).

Historical Background

RAB proteins are members of the RAS superfamily of small GTPases, with which they share sequence and structural homology. RAS isoforms were first identified in cancer-causing viruses and subsequently as oncogenes, prompting substantial interest. Subfamilies of the RAS GTPases include the RAB, RHO, ARF, RAP, and RAN proteins of which RABs are the largest group (Takai et al. 2001). Early work in yeast identified essential roles for the RABs Ypt1p and Sec4p in pre- and post-Golgi membrane trafficking (Salminen and Novick 1987; Segev et al. 1988). Efforts to clone other members of the RAB gene family quickly established that this family had undergone significant expansion in higher eukaryotes. As each new RAB was discovered, it also became clear that different RAB proteins could adopt specific subcellular localizations, associating with particular membrane...

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

References

  • Aligianis IA, Johnson CA, Gissen P, Chen D, Hampshire D, Hoffmann K, et al. Mutations of the catalytic subunit of RAB3GAP cause Warburg micro syndrome. Nat Genet. 2005;37:221–3. doi:10.1038/ng1517.

    Article  CAS  PubMed  Google Scholar 

  • Barr FA. Review series: Rab GTPases and membrane identity: causal or inconsequential? J Cell Biol. 2013;202:191–9. doi:10.1083/jcb.201306010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, et al. Loss-of-function mutations in RAB18 cause Warburg micro syndrome. Am J Hum Genet. 2011;88:499–507. doi:10.1016/j.ajhg.2011.03.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borck G, Wunram H, Steiert A, Volk AE, Korber F, Roters S, et al. A homozygous RAB3GAP2 mutation causes Warburg micro syndrome. Hum Genet. 2011;129:45–50. doi:10.1007/s00439-010-0896-2.

    Article  PubMed  Google Scholar 

  • Carpanini SM, McKie L, Thomson D, Wright AK, Gordon SL, Roche SL, et al. A novel mouse model of Warburg Micro syndrome reveals roles for RAB18 in eye development and organisation of the neuronal cytoskeleton. Dis Model Mech. 2014;7:711–22. doi:10.1242/dmm.015222.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chavrier P, Simons K, Zerial M. The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach. Gene. 1992;112:261–4.

    Article  CAS  PubMed  Google Scholar 

  • Cheng CY, Wu JC, Tsai JW, Nian FS, Wu PC, Kao LS, et al. ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon degeneration caused by a deletion in Rab18. Exp Neurol. 2015;267:143–51. doi:10.1016/j.expneurol.2015.03.003.

    Article  CAS  PubMed  Google Scholar 

  • Cho NJ, Lee C, Pang PS, Pham EA, Fram B, Nguyen K, et al. Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A ligand and mediates replication of the viral genome. Gastroenterology. 2015;148:616–25. doi:10.1053/j.gastro.2014.11.043.

    Article  CAS  PubMed  Google Scholar 

  • Dejgaard SY, Murshid A, Erman A, Kizilay O, Verbich D, Lodge R, et al. Rab18 and Rab43 have key roles in ER-Golgi trafficking. J Cell Sci. 2008;121:2768–81. doi:10.1242/jcs.021808.

    Article  CAS  PubMed  Google Scholar 

  • Dopie J, Rajakyla EK, Joensuu MS, Huet G, Ferrantelli E, Xie T, et al. Genome-wide RNAi screen for nuclear actin reveals a network of cofilin regulators. J Cell Sci. 2015;128:2388–400. doi:10.1242/jcs.169441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eastman SW, Yassaee M, Bieniasz PD. A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover. J Cell Biol. 2009;184:881–94. doi:10.1083/jcb.200808041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukui K, Sasaki T, Imazumi K, Matsuura Y, Nakanishi H, Takai Y. Isolation and characterization of a GTPase activating protein specific for the Rab3 subfamily of small G proteins. J Biol Chem. 1997;272:4655–8.

    Article  CAS  PubMed  Google Scholar 

  • Gerondopoulos A, Bastos RN, 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. doi:10.1083/jcb.201403026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillingham AK, Sinka R, Torres IL, Lilley KS, Munro S. Toward a comprehensive map of the effectors of rab GTPases. Dev Cell. 2014;31:358–73. doi:10.1016/j.devcel.2014.10.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, et al. Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in Warburg micro syndrome and Martsolf syndrome. Hum Mutat. 2013;34:686–96. doi:10.1002/humu.22296.

    Article  CAS  PubMed  Google Scholar 

  • Handley MT, Carpanini SM, Mali GR, Sidjanin DJ, Aligianis IA, Jackson IJ, et al. Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation. Open Biol. 2015;5:150047. doi:10.1098/rsob.150047.

    Article  PubMed  PubMed Central  Google Scholar 

  • Klopper TH, Kienle N, Fasshauer D, Munro S. Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis. BMC Biol. 2012;10:71. doi:10.1186/1741-7007-10-71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung KF, Baron R, Ali BR, Magee AI, Seabra MC. Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation. J Biol Chem. 2007;282:1487–97. doi:10.1074/jbc.M605557200.

    Article  CAS  PubMed  Google Scholar 

  • Liegel RP, Handley MT, Ronchetti A, Brown S, Langemeyer L, Linford A, et al. Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet. 2013;93:1001–14. doi:10.1016/j.ajhg.2013.10.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Zhang J, Li Y, Wang L, Sui B, Dai D. MiR-455-5p acts as a novel tumor suppressor in gastric cancer by down-regulating RAB18. Gene. 2016. doi:10.1016/j.gene.2016.07.034.

    Google Scholar 

  • Martin S, Driessen K, Nixon SJ, Zerial M, Parton RG. Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. J Biol Chem. 2005;280:42325–35. doi:10.1074/jbc.M506651200.

    Article  CAS  PubMed  Google Scholar 

  • Mhlanga-Mutangadura T, Johnson GS, Ashwini A, Shelton GD, Wennogle SA, Johnson GC, et al. A Homozygous RAB3GAP1:c.743delC mutation in Rottweilers with neuronal vacuolation and spinocerebellar degeneration. J Vet Int Med. 2016a;30:813–8. doi:10.1111/jvim.13921.

    Article  CAS  Google Scholar 

  • Mhlanga-Mutangadura T, Johnson GS, Schnabel RD, Taylor JF, Johnson GC, Katz ML, et al. A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs. Neurobiol Dis. 2016b;86:75–85. doi:10.1016/j.nbd.2015.11.016.

    Article  CAS  PubMed  Google Scholar 

  • Muller M, Pym EC, Tong A, Davis GW. Rab3-GAP controls the progression of synaptic homeostasis at a late stage of vesicle release. Neuron. 2011;69:749–62. doi:10.1016/j.neuron.2011.01.025.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nachmias D, Sklan EH, Ehrlich M, Bacharach E. Human immunodeficiency virus type 1 envelope proteins traffic toward virion assembly sites via a TBC1D20/Rab1-regulated pathway. Retrovirology. 2012;9:7. doi:10.1186/1742-4690-9-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagano F, Sasaki T, Fukui K, Asakura T, Imazumi K, Takai Y. Molecular cloning and characterization of the noncatalytic subunit of the Rab3 subfamily-specific GTPase-activating protein. J Biol Chem. 1998;273:24781–5.

    Article  CAS  PubMed  Google Scholar 

  • Ozeki S, Cheng J, Tauchi-Sato K, Hatano N, Taniguchi H, Fujimoto T. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J Cell Sci. 2005;118:2601–11. doi:10.1242/jcs.02401.

    Article  CAS  PubMed  Google Scholar 

  • Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600. doi:10.1016/j.neuron.2004.10.023.

    Article  CAS  PubMed  Google Scholar 

  • Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, et al. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet. 2002;31:347–8. doi:10.1038/ng937.

    CAS  PubMed  Google Scholar 

  • Pulido MR, Diaz-Ruiz A, Jimenez-Gomez Y, Garcia-Navarro S, Gracia-Navarro F, Tinahones F, et al. Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity. PLoS One. 2011;6:e22931. doi:10.1371/journal.pone.0022931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakane A, Manabe S, Ishizaki H, Tanaka-Okamoto M, Kiyokage E, Toida K, et al. Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3. Proc Natl Acad Sci U S A. 2006;103:10029–34. doi:10.1073/pnas.0600304103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salloum S, Wang H, Ferguson C, Parton RG, Tai AW. Rab18 binds to hepatitis C virus NS5A and promotes interaction between sites of viral replication and lipid droplets. PLoS Pathog. 2013;9:e1003513. doi:10.1371/journal.ppat.1003513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salminen A, Novick PJ. A ras-like protein is required for a post-Golgi event in yeast secretion. Cell. 1987;49:527–38.

    Article  CAS  PubMed  Google Scholar 

  • Schafer U, Seibold S, Schneider A, Neugebauer E. Isolation and characterisation of the human rab18 gene after stimulation of endothelial cells with histamine. FEBS Lett. 2000;466:148–54.

    Article  CAS  PubMed  Google Scholar 

  • Segev N, Mulholland J, Botstein D. The yeast GTP-binding YPT1 protein and a mammalian counterpart are associated with the secretion machinery. Cell. 1988;52:915–24.

    Article  CAS  PubMed  Google Scholar 

  • Sidjanin DJ, Park AK, Ronchetti A, Martins J, Jackson WT. TBC1D20 mediates autophagy as a key regulator of autophagosome maturation. Autophagy. 2016:1–17. doi:10.1080/15548627.2016.1199300.

    Google Scholar 

  • Spang N, Feldmann A, Huesmann H, Bekbulat F, Schmitt V, Hiebel C, et al. RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy. Autophagy. 2014;10:2297–309. doi:10.4161/15548627.2014.994359.

    Article  CAS  PubMed  Google Scholar 

  • Steger M, Tonelli F, Ito G, Davies P, Trost M, Vetter M, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife. 2016;5. doi:10.7554/eLife.12813.

    Google Scholar 

  • Tagaya M, Arasaki K, Inoue H, Kimura H. Moonlighting functions of the NRZ (mammalian Dsl1) complex. Front Cell Dev Biol. 2014;2:25. doi:10.3389/fcell.2014.00025.

    Article  PubMed  PubMed Central  Google Scholar 

  • Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81:153–208.

    CAS  PubMed  Google Scholar 

  • Tang WC, Lin RJ, Liao CL, Lin YL. Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication. J Virol. 2014;88:6793–804. doi:10.1128/JVI.00045-14.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vazquez-Martinez R, Cruz-Garcia D, Duran-Prado M, Peinado JR, Castano JP, Malagon MM. Rab18 inhibits secretory activity in neuroendocrine cells by interacting with secretory granules. Traffic. 2007;8:867–82. doi:10.1111/j.1600-0854.2007.00570.x.

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-Martinez R, Martinez-Fuentes AJ, Pulido MR, Jimenez-Reina L, Quintero A, Leal-Cerro A, et al. Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion. J Clin Endocrinol Metab. 2008;93:2269–76. doi:10.1210/jc.2007-1893.

    Article  CAS  PubMed  Google Scholar 

  • Wiedmer M, Oevermann A, Borer-Germann SE, Gorgas D, Shelton GD, Drogemuller M, et al. A RAB3GAP1 SINE insertion in Alaskan huskies with polyneuropathy, ocular abnormalities, and neuronal vacuolation (POANV) resembling human warburg micro syndrome 1 (WARBM1). G3. 2016;6:255–62. doi:10.1534/g3.115.022707.

    Article  Google Scholar 

  • Wu Q, Sun X, Yue W, Lu T, Ruan Y, Chen T, et al. RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex. Mol Brain. 2016;9:19. doi:10.1186/s13041-016-0198-2.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu H, Leaf DS, Moore HP. Gene cloning and characterization of a GTP-binding Rab protein from mouse pituitary AtT-20 cells. Gene. 1993;132:273–8.

    Article  CAS  PubMed  Google Scholar 

  • Zenner HL, Yoshimura S, Barr FA, Crump CM. Analysis of Rab GTPase-activating proteins indicates that Rab1a/b and Rab43 are important for herpes simplex virus 1 secondary envelopment. J Virol. 2011;85:8012–21. doi:10.1128/JVI.00500-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong K, Chen K, Han L, Li B. MicroRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18. BMC Cancer. 2014;14:703. doi:10.1186/1471-2407-14-703.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark T. Handley Dr .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Handley, M.T. (2016). RAB18. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_298-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_298-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6438-9

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics