Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Rab27

  • Mai E. Oguchi
  • Mitsunori Fukuda
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101791

Synonyms

 Ash;  c25KG;  Rab27a;  Rab27A;  Rab27b;  Rab27B;  Ram

Historical Background

Rab27 is a member of the Rab family small GTPases, which constitute the largest family of membrane trafficking proteins in all eukaryotes. Rab27 is widely conserved in metazoans, including Caenorhabditis elegans (nematode), Drosophila melanogaster (fruit fly), and Loligo pealei (long-finned squid), and is conserved in all species of vertebrates, but it is not found in yeasts or plants (Diekmann et al. 2011). Like other small GTPases, Rab27 functions as a switch molecule by cycling between a GTP-bound active state and a GDP-bound inactive state (Fig. 1). In its GTP-bound active state, Rab27 has been shown to regulate a variety of secretory pathways by recruiting specific effector molecules (Fukuda 2013). Although invertebrates appear to contain a single Rab27 isoform, vertebrates contain two Rab27 isoforms, Rab27A and Rab27B, which exhibit more than 70% identity at the amino acid level. RAB27Ais the...
This is a preview of subscription content, log in to check access.

References

  1. Arimura N, Kimura T, Nakamuta S, Taya S, Funahashi Y, Hattori A, et al. Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell. 2009;16:675–86. doi:10.1016/j.devcel.2009.03.005. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Diekmann Y, Seixas E, Gouw M, Tavares-Cadete F, Seabra MC, Pereira-Leal JB. Thousands of rab GTPases for the cell biologist. PLoS Comput Biol. 2011;7:e1002217. doi:10.1371/journal.pcbi.1002217. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Elstak ED, Neeft M, Nehme NT, Voortman J, Cheung M, Goodarzifard M, et al. The munc13-4-rab27 complex is specifically required for tethering secretory lysosomes at the plasma membrane. Blood. 2011;118:1570–8. doi:10.1182/blood-2011-02-339523. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Figueiredo AC, Wasmeier C, Tarafder AK, Ramalho JS, Baron RA, Seabra MC. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem. 2008;283:23209–16. doi:10.1074/jbc.M804134200. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Fukuda M. TBC proteins: GAPs for mammalian small GTPase Rab? Biosci Rep. 2011;31:159–68. doi:10.1042/BSR20100112. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Fukuda M. Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic. 2013;14:949–63. doi:10.1111/tra.12083. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gálvez-Santisteban M, Rodriguez-Fraticelli AE, Bryant DM, Vergarajauregui S, Yasuda T, Bañón-Rodríguez I, et al. Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nat Cell Biol. 2012;14:838–49. doi:10.1038/ncb2541. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T. Granuphilin molecularly docks insulin granules to the fusion machinery. J Cell Biol. 2005;171:99–109. doi:10.1083/jcb.200505179. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Imai A, Yoshie S, Ishibashi K, Haga-Tsujimura M, Nashida T, Shimomura H, et al. EPI64 protein functions as a physiological GTPase-activating protein for Rab27 protein and regulates amylase release in rat parotid acinar cells. J Biol Chem. 2011;286:33854–62. doi:10.1074/jbc.M111.281394. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Itoh T, Fukuda M. Identification of EPI64 as a GTPase-activating protein specific for Rab27A. J Biol Chem. 2006;281:31823–31. doi:10.1074/jbc.M603808200. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Johnson JL, Brzezinska AA, Tolmachova T, Munafo DB, Ellis BA, Seabra MC, et al. Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic. 2010;11:533–47. doi:10.1111/j.1600-0854.2009.01029.x. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Kuroda TS, Fukuda M. Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Nat Cell Biol. 2004;6:1195–203. doi:10.1038/ncb1197. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kurowska M, Goudin N, Nehme NT, Court M, Garin J, Fischer A, et al. Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex. Blood. 2012;26(119):3879–89. doi:10.1182/blood-2011-09-382556. PubMed.CrossRefGoogle Scholar
  14. Mahoney TR, Liu Q, Itoh T, Luo S, Hadwiger G, Vincent R, et al. Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans. Mol Biol Cell. 2006;17:2617–25. doi:10.1091/mbc.E05-12-1170. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  15. McGrath JA, Stone KL, Begum R, Simpson MA, Dopping-Hepenstal PJ, Liu L, et al. Germline mutation in EXPH5 implicates the Rab27B effector protein Slac2-b in inherited skin fragility. Am J Hum Genet. 2012;91:1115–21. doi:10.1016/j.ajhg.2012.10.012. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Ostrowski M, Carmo NB, 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. doi:10.1038/ncb2000. PubMed.CrossRefPubMedGoogle Scholar
  17. Saegusa C, Tanaka T, Tani S, Itohara S, Mikoshiba K, Fukuda M. Decreased basal mucus secretion by Slp2-a-deficient gastric surface mucous cells. 2006;11:623–31. doi: 10.1111/j.1365-2443.2006.00964.x. PubMedCrossRefPubMedPubMedCentralGoogle Scholar
  18. Singh RK, Mizuno K, Wasmeier C, Wavre-Shapton ST, Recchi C, Catz SD, et al. Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. FEBS J. 2013;280:892–903. doi:10.1111/febs.12081. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Van Gele M, Dynoodt P, Lambert J. Griscelli syndrome: a model system to study vesicular trafficking. Pigment Cell Melanoma Res. 2009;22:268–82. doi:10.1111/j.1755-148X.2009.00558.x. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Yamaoka M, Ishizaki T, Kimura T. Interplay between Rab27a effectors in pancreatic β-cells. World J Diabetes. 2015;6:508–16. doi:10.4239/wjd.v6.i3.508. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Yasuda T, Fukuda M. Slp2-a controls renal epithelial cell size through regulation of Rap–ezrin signaling independently of Rab27. J Cell Sci. 2014;127:557–70. doi:10.1242/jcs.134056. PubMed.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life SciencesTohoku UniversitySendaiJapan