title: PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation.
abstract: Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation.
authors.affiliation: College of Biological Sciences China Agriculture University, Beijing, China National Institute of Biological Sciences, Beijing, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Shiya
authors.initials: S
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Physiology, School of Medicine and Institute for Integrated Medical Sciences Tokyo Women's Medical University, Shinjuku-ku Tokyo, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.affiliation: Department of Physiology, School of Medicine and Institute for Integrated Medical Sciences Tokyo Women's Medical University, Shinjuku-ku Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing, China wangxiaochen@nibs.ac.cn.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C532246:mtm-3 protein, C elegans; C061816:phosphatidylinositol-3-phosphatase
keywords: Caenorhabditis elegans; MTM‐3; PtdIns3P; autolysosome; autophagy