| First Author | Aoyagi K | Year | 2018 |
| Journal | Endocrinology | Volume | 159 |
| Issue | 11 | Pages | 3674-3688 |
| PubMed ID | 30215699 | Mgi Jnum | J:266554 |
| Mgi Id | MGI:6220765 | Doi | 10.1210/en.2018-00447 |
| Citation | Aoyagi K, et al. (2018) VAMP7 Regulates Autophagosome Formation by Supporting Atg9a Functions in Pancreatic beta-Cells From Male Mice. Endocrinology 159(11):3674-3688 |
| abstractText | Dysfunctional mitochondria are observed in beta-cells of diabetic patients, which are eventually removed by autophagy. Vesicle-associated membrane protein (VAMP)7, a vesicular SNARE protein, regulates autophagosome formation to maintain mitochondrial homeostasis and control insulin secretion in pancreatic beta-cells. However, its molecular mechanism is largely unknown. In this study, we investigated the molecular mechanism of VAMP7-dependent autophagosome formation using VAMP7-deficient beta-cells and beta-cell-derived Min6 cells. VAMP7 localized in autophagy-related (Atg)9a-resident vesicles of recycling endosomes (REs), which contributed to autophagosome formation, and it interacted with Hrb, Syntaxin16, and SNAP-47. Hrb recruited VAMP7 and Atg9a from the plasma membrane to REs. Syntaxin16 and SNAP-47 mediated autophagosome formation at a step later than the proper localization of VAMP7 to Atg9a-resident vesicles. Knockdown of Hrb, Syntaxin16, and SNAP-47 resulted in defective autophagosome formation, accumulation of dysfunctional mitochondria, and impairment of glucose-stimulated insulin secretion. Our data indicate that VAMP7 and Atg9a are initially recruited to REs to organize VAMP7 and Atg9a-resident vesicles in an Hrb-dependent manner. Additionally, VAMP7 forms a SNARE complex with Syntaxin16 and SNAP-47, which may cause fusions of Atg9a-resident vesicles during autophagosome formation. Thus, VAMP7 participates in autophagosome formation by supporting Atg9a functions that contribute to maintenance of mitochondrial quality. |
