title: Rab27a, actin and beta-cell endocytosis.
abstract: The output and time-course of insulin release from pancreatic beta-cells are elegantly controlled. The secretory process comprises pre-exocytotic stages, exocytosis and post-exocytotic stages. The small GTPase Rab27a is known to regulate pre-exocytotic stages that determine the size of the readily-releasable pool of insulin granules. GTP-Rab27a and its specific effectors are responsible for this process like other GTPases. Recently, we searched for Rab27a-interacting proteins and identified coronin 3. Unexpectedly, coronin 3 only bound GDP-Rab27a and this interaction regulated post-exocytotic stages via reorganization of the actin cytoskeleton. Since glucose converts Rab27a from the GTP- to GDP-bound form, we suggested that Rab27a plays a crucial role in stimulus-endocytosis coupling in pancreatic beta-cells, and that this is the key molecule for membrane recycling of insulin granules. In this review, we provide an overview of the roles of Rab27a and its GTP- and GDP-dependent effectors in the insulin secretory pathway of pancreatic beta-cells.
authors.affiliation: Department of Pharmacology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kimura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Niki
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D004705:Endocytosis; D005089:Exocytosis / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000199:Actins; D007328:Insulin; D008840:Microfilament Proteins; D000075745:rab27 GTP-Binding Proteins; C072061:coronin proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins