PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation |
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| Authors: | Yanwei Wu Shiya Cheng Hongyu Zhao Wei Zou Sawako Yoshina Shohei Mitani Hong Zhang Xiaochen Wang |
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| Institution: | 1. College of Biological Sciences, China Agriculture University, , Beijing, China;2. National Institute of Biological Sciences, , Beijing, China;3. State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, , Beijing, China;4. Department of Physiology, School of Medicine and Institute for Integrated Medical Sciences, Tokyo Women's Medical University, , Shinjuku‐ku, Tokyo, Japan |
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| 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. |
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| Keywords: | autolysosome autophagy
Caenorhabditis elegans
MTM‐3 PtdIns3P |
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