Atg16L1 is an essential factor for canonical autophagy, a conserved bulk degradation system in all eukaryotes. Atg16L1 forms a complex with Atg12-conjugated Atg5, i.e., an Atg16L1-5-12 complex, and promotes elongation of isolation membranes possibly by recruiting LC3 and by facilitating its lipidation. Because of its critical role in canonical autophagy, cells from Atg16L1-deficient mice exhibit complete loss of autophagosome formation. Interestingly, the intestinal Paneth cells of Atg16L1-deficient mice exhibit a secretion defect, but the mechanism by which Atg16L1 regulates the secretory pathway is poorly understood. We recently reported the finding that Atg16L1 localizes on hormone-containing dense-core vesicles in neuroendocrine PC12 cells independent of canonical autophagy and that small GTPase Rab33A recruits the Atg16L1-5-12 complex to dense-core vesicles. We also found that knockdown of Atg16L1 in PC12 cells caused a dramatic reduction in hormone secretion independent of the autophagic activity of the cells. Our findings indicate that, in addition to its role in autophagy, Atg16L1 (or the Atg16L1-5-12 complex) regulates hormone secretion from dense-core vesicles, most likely by acting as a Rab33A effector in particular cell types, including PC12 cells.
|ホスト出版物のタイトル||Role of Autophagy in Therapeutic Applications|
|出版ステータス||Published - 2015 2 18|
ASJC Scopus subject areas
- Immunology and Microbiology(all)