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PI 3 P phosphatase activity is required for autophagosome maturation and autolysosome formation
Author(s) -
Wu Yanwei,
Cheng Shiya,
Zhao Hongyu,
Zou Wei,
Yoshina Sawako,
Mitani Shohei,
Zhang Hong,
Wang Xiaochen
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201438618
Subject(s) - autophagy , autophagosome , microbiology and biotechnology , phosphatase , phosphatidylinositol , chemistry , phagosome , caenorhabditis elegans , kinase , phosphorylation , biology , biochemistry , intracellular , apoptosis , gene
Autophagosome formation is promoted by the PI 3 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.