Wu Yanwei, Cheng Shiya, Zhao Hongyu, Zou Wei, Yoshina Sawako, Mitani Shohei, Zhang Hong, Wang Xiaochen
College of Biological Sciences China Agriculture University, Beijing, China National Institute of Biological Sciences, Beijing, China.
National Institute of Biological Sciences, Beijing, China.
EMBO Rep. 2014 Sep;15(9):973-81. doi: 10.15252/embr.201438618. Epub 2014 Aug 14.
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.
自噬体的形成由PI3激酶复合物促进，并受肌管蛋白磷酸酶负调控，这表明局部磷脂酰肌醇3-磷酸（PtdIns3P）水平的调节对于自噬的早期阶段很重要。在这里，我们表明秀丽隐杆线虫的肌管蛋白磷酸酶MTM-3在自噬后期催化PtdIns3P周转。MTM-3在ATG-2/EPG-6复合物的下游和EPG-5的上游起作用，以促进自噬体成熟为自溶酶体。MTM-3通过PtdIns3P被募集到自噬体上，MTM-3的缺失导致ATG-18以PtdIns3P依赖的方式增加自噬关联。我们的数据揭示了PtdIns3P周转在自噬体成熟和/或自溶酶体形成中的关键作用。
