Interplay Between Rab27a Effectors in Pancreatic β-cells

Overview

Journal World J Diabetes

Publisher Baishideng Publishing Group

Specialty Endocrinology

Date 2015 Apr 22

PMID 25897360

Citations 9

Authors

Mami Yamaoka

Toshimasa Ishizaki

Toshihide Kimura

Affiliations

Soon will be listed here.

Abstract

The small GTPase Rab27a is a member of the Rab family that is involved in membrane trafficking in various kinds of cells. Rab27a has GTP- and GDP-bound forms, and their interconversion regulates intracellular signaling pathways. Typically, only a GTP-bound GTPase binds its specific effectors with the resulting downstream signals controlling specific cellular functions. We previously identified novel Rab27a-interacting proteins. Surprisingly, some of these proteins interacted with GDP-bound Rab27a. The present study reviews recent progress in our understanding of the roles of Rab27a and its effectors in the secretory process. In pancreatic β-cells, GTP-bound Rab27a regulates insulin secretion at the pre-exocytotic stages via its GTP-specific effectors such as Exophilin8/Slac2-c/MyRIP and Slp4/Granuphilin. Glucose stimulation causes insulin exocytosis. Glucose stimulation also converts Rab27a from its GTP- to its GDP-bound form. GDP-bound Rab27a interacts with GDP-specific effectors and controls endocytosis of the secretory membrane. Thus, Rab27a cycling between GTP- and GDP-bound forms synchronizes with the recycling of secretory membrane to re-use the membrane and keep the β-cell volume constant.

Citing Articles

Identifying of immune-associated genes for assessing the obesity-associated risk to the offspring in maternal obesity: A bioinformatics and machine learning.

Shang Y, Wang X, Su S, Ji F, Shao D, Duan C CNS Neurosci Ther. 2024; 30(3):e14700.

PMID: 38544384 PMC: 10973700. DOI: 10.1111/cns.14700.

A conserved electrostatic membrane-binding surface in synaptotagmin-like proteins revealed using molecular phylogenetic analysis and homology modeling.

Chon N, Tran S, Miller C, Lin H, Knight J Protein Sci. 2023; 33(1):e4850.

PMID: 38038838 PMC: 10731544. DOI: 10.1002/pro.4850.

A Conserved Electrostatic Membrane-Binding Surface in Synaptotagmin-Like Proteins Revealed Using Molecular Phylogenetic Analysis and Homology Modeling.

Chon N, Tran S, Miller C, Lin H, Knight J bioRxiv. 2023; .

PMID: 37502952 PMC: 10369986. DOI: 10.1101/2023.07.13.548768.

Emerging Roles of Small GTPases in Islet β-Cell Function.

Veluthakal R, Thurmond D Cells. 2021; 10(6).

PMID: 34203728 PMC: 8232272. DOI: 10.3390/cells10061503.

Multivalent lipid targeting by the calcium-independent C2A domain of synaptotagmin-like protein 4/granuphilin.

Alnaas A, Watson-Siriboe A, Tran S, Negussie M, Henderson J, Osterberg J J Biol Chem. 2020; 296:100159.

PMID: 33277360 PMC: 7857503. DOI: 10.1074/jbc.RA120.014618.

References

Chen D, Guo J, Miki T, Tachibana M, Gahl W . Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets. Biochem Mol Med. 1997; 60(1):27-37. DOI: 10.1006/bmme.1996.2559. View

Zerial M, McBride H . Rab proteins as membrane organizers. Nat Rev Mol Cell Biol. 2001; 2(2):107-17. DOI: 10.1038/35052055. View

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(8):4655-8. DOI: 10.1074/jbc.272.8.4655. View

Kuroda S, Fukata M, Nakagawa M, Fujii K, Nakamura T, Ookubo T . Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- mediated cell-cell adhesion. Science. 1998; 281(5378):832-5. DOI: 10.1126/science.281.5378.832. View

Kahn S . Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001; 86(9):4047-58. DOI: 10.1210/jcem.86.9.7713. View

Nevins A, Thurmond D . Glucose regulates the cortical actin network through modulation of Cdc42 cycling to stimulate insulin secretion. Am J Physiol Cell Physiol. 2003; 285(3):C698-710. DOI: 10.1152/ajpcell.00093.2003. View

Menasche G, Pastural E, Feldmann J, Certain S, Ersoy F, Dupuis S . Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet. 2000; 25(2):173-6. DOI: 10.1038/76024. View

Hou Y, Chen X, Tolmachova T, Ernst S, Williams J . EPI64B acts as a GTPase-activating protein for Rab27B in pancreatic acinar cells. J Biol Chem. 2013; 288(27):19548-57. PMC: 3707656. DOI: 10.1074/jbc.M113.472134. View

Stinchcombe J, Barral D, Mules E, Booth S, Hume A, Machesky L . Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J Cell Biol. 2001; 152(4):825-34. PMC: 2195783. DOI: 10.1083/jcb.152.4.825. View

10.

Fukata M, Nakagawa M, Kaibuchi K . Roles of Rho-family GTPases in cell polarisation and directional migration. Curr Opin Cell Biol. 2003; 15(5):590-7. DOI: 10.1016/s0955-0674(03)00097-8. View

11.

Briggs M, Sacks D . IQGAP proteins are integral components of cytoskeletal regulation. EMBO Rep. 2003; 4(6):571-4. PMC: 1319206. DOI: 10.1038/sj.embor.embor867. View

12.

Kondo H, Shirakawa R, Higashi T, Kawato M, Fukuda M, Kita T . Constitutive GDP/GTP exchange and secretion-dependent GTP hydrolysis activity for Rab27 in platelets. J Biol Chem. 2006; 281(39):28657-65. DOI: 10.1074/jbc.M603227200. View

13.

Westbroek W, Lambert J, Naeyaert J . The dilute locus and Griscelli syndrome: gateways towards a better understanding of melanosome transport. Pigment Cell Res. 2001; 14(5):320-7. DOI: 10.1034/j.1600-0749.2001.140503.x. View

14.

Shirane M, Nakayama K . Protrudin induces neurite formation by directional membrane trafficking. Science. 2006; 314(5800):818-21. DOI: 10.1126/science.1134027. View

15.

Galletta B, Chuang D, Cooper J . Distinct roles for Arp2/3 regulators in actin assembly and endocytosis. PLoS Biol. 2008; 6(1):e1. PMC: 2156081. DOI: 10.1371/journal.pbio.0060001. View

16.

Ashcroft F, Rorsman P . Molecular defects in insulin secretion in type-2 diabetes. Rev Endocr Metab Disord. 2004; 5(2):135-42. DOI: 10.1023/B:REMD.0000021435.87776.a7. View

17.

Kimura T, Niki I . Rab27a in pancreatic beta-cells, a busy protein in membrane trafficking. Prog Biophys Mol Biol. 2011; 107(2):219-23. DOI: 10.1016/j.pbiomolbio.2011.06.016. View

18.

Imai A, Fukuda M, Yoshie S, Nashida T, Shimomura H . Redistribution of Rab27-specific effector Slac2-c, but not Slp4-a, after isoproterenol-stimulation in rat parotid acinar cells. Arch Oral Biol. 2009; 54(4):361-8. DOI: 10.1016/j.archoralbio.2008.12.007. View

19.

Menasche G, Ho C, Sanal O, Feldmann J, Tezcan I, Ersoy F . Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. 2003; 112(3):450-6. PMC: 166299. DOI: 10.1172/JCI18264. View

20.

Noritake J, Fukata M, Sato K, Nakagawa M, Watanabe T, Izumi N . Positive role of IQGAP1, an effector of Rac1, in actin-meshwork formation at sites of cell-cell contact. Mol Biol Cell. 2003; 15(3):1065-76. PMC: 363077. DOI: 10.1091/mbc.e03-08-0582. View