GDP-bound Rab27a regulates clathrin disassembly through HSPA8 after insulin secretion

• Published in: Archives of biochemistry and biophysics 2023-11, Vol.749, p.109789-109789, Article 109789
• Main Authors: Kodera, Soshiro, Kimura, Toshihide, Nishioka, Tomoki, Kaneko, Yukiko K., Yamaguchi, Momoka, Kaibuchi, Kozo, Ishikawa, Tomohisa
• Format: Article
• Language: English
• Subjects: Clathrin; Clathrin - metabolism; Diabetes; Endocytosis; Endocytosis - physiology; Glucose - metabolism; HSPA8; Insulin; Insulin - metabolism; Insulin Secretion; rab GTP-Binding Proteins - metabolism; rab27 GTP-Binding Proteins - metabolism; Rab27a
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2023.109789

Clathrin-dependent endocytosis is a key process for secretory cells, in which molecules on the plasma membrane are both degraded and recycled in a stimulus-dependent manner. There are many reports showing that disruption of endocytosis is involved in the onset of various diseases. Recently, it has been reported that such disruption in pancreatic β-cells causes impaired insulin secretion and might be associated with the pathology of diabetes mellitus. Compared with exocytosis, there are few reports on the molecular mechanism of endocytosis in pancreatic β-cells. We previously reported that GDP-bound Rab27a regulates endocytosis through its GDP-dependent effectors after insulin secretion. In this study, we identified heat shock protein family A member 8 (HSPA8) as a novel interacting protein for GDP-bound Rab27a. HSPA8 directly bound GDP-bound Rab27a via the β2 region of its substrate binding domain (SBD). The β2 fragment was capable of inhibiting the interaction between HSPA8 and GDP-bound Rab27a, and suppressed glucose-induced clathrin-dependent endocytosis in pancreatic β-cells. The region also affected clathrin dynamics on purified clathrin-coated vesicles (CCVs). These results suggest that the interaction between GDP-bound Rab27a and HSPA8 regulates clathrin disassembly from CCVs and subsequent vesicle transport. The regulatory stages in endocytosis by HSPA8 differ from those for other GDP-bound Rab27a effectors. This study shows that GDP-bound Rab27a dominantly regulates each stage in glucose-induced endocytosis through its specific effectors in pancreatic β-cells. [Display omitted] •HSPA8 is a novel GDP-bound Rab27a-interacting protein.•The interaction between GDP-bound Rab27a and HSPA8 is essential for glucose-induced endocytosis.•GDP-bound Rab27a regulates CCVs through HSPA8.•The endocytosis-related interaction affects glucose-stimulated insulin secretion.