title: Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity.
abstract: Autophagy is a bulk degradation system in all eukaryotic cells and regulates a variety of biological activities in higher eukaryotes. Recently involvement of autophagy in the regulation of the secretory pathway has also been reported, but the molecular mechanism linking autophagy with the secretory pathway remains largely unknown. Here we show that Atg16L1, an essential protein for canonical autophagy, is localized on hormone-containing dense-core vesicles in neuroendocrine PC12 cells and that knockdown of Atg16L1 causes a dramatic reduction in the level of hormone secretion independently of autophagic activity. We also find that Atg16L1 interacts with the small GTPase Rab33A and that this interaction is required for the dense-core vesicle localization of Atg16L1 in PC12 cells. Our findings indicate that Atg16L1 regulates not only autophagy in all cell types, but also secretion from dense-core vesicles, presumably by acting as a Rab33A effector, in particular cell types.
authors: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan.
authors: Koutaro
authors: K
authors: Ishibashi
authors: Takefumi
authors: T
authors: Uemura
authors: Satoshi
authors: S
authors: Waguri
authors: Mitsunori
authors: M
authors: Fukuda
mesh_terms: D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis; D051379:Mice; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009478:Neuropeptide Y / Q000378:metabolism*; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human; C577013:Atg16L1 protein, rat; D019204:GTP-Binding Proteins; C514094:Rab33A protein, rat; D020691:rab GTP-Binding Proteins