Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2015; 6(3): 508-516
Published online Apr 15, 2015. doi: 10.4239/wjd.v6.i3.508
Interplay between Rab27a effectors in pancreatic β-cells
Mami Yamaoka, Toshimasa Ishizaki, Toshihide Kimura
Mami Yamaoka, Toshimasa Ishizaki, Toshihide Kimura, Department of Pharmacology, Oita University Faculty of Medicine, Oita 879-5593, Japan
Author contributions: Yamaoka M, Ishizaki T and Kimura T developed the concept and wrote the paper.
Supported by JSPS KAKENHI Grant, Nos. 19790636, 21790876, 23791039, and 26461342; the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University, Takeda Science Foundation, Novo Nordisk Pharma, Oita Broadcasting System Cultural Foundation, and Research Fund at the Discretion of the President, Oita University.
Conflict-of-interest: The authors declare no competing financial interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Toshihide Kimura, Associate Professor, Department of Pharmacology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan. t-kimura@oita-u.ac.jp
Telephone: +81-97-5865722 Fax: +81-97-5865729
Received: August 25, 2014
Peer-review started: August 25, 2014
First decision: December 17, 2014
Revised: December 24, 2014
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: April 15, 2015
Processing time: 237 Days and 18.4 Hours
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.

Keywords: Insulin; Exocytosis; Endocytosis; Rab27a; IQGAP1; Coronin 3; Glucose; Small GTPase

Core tip: The small GTPase Rab27a is a member of the Rab family that is involved in membrane trafficking in pancreatic β-cells. GTP-bound Rab27a regulates insulin secretion at 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.