TMEM166/EVA1A interacts with ATG16L1 and induces autophagosome formation and cell death

• DOI: 10.1038/cddis.2016.230
• Publication Date: 2016-08-04T12:47:47Z
• Authors: Jia Hu; Ge Li; Liujing Qu; Ning Li; Wei Liu; Dan xia; Beiqi Hongdu; Xin Lin; Chentong Xu; Yaxin Lou; Qihua He; Dalong Ma; Yingyu Chen
• Keywords: ATG16L1; Autophagosome; BECN1; ULK1; ATG12

Abstract The formation of the autophagosome is controlled by an orderly action ATG proteins. However, how these proteins are recruited to autophagic membranes remain poorly clarified. In this study, we have provided a line evidence confirming that EVA1A (eva-1 homolog A)/TMEM166 (transmembrane protein 166) associated with autophagosomal membrane development. This notion based on dotted structures colocalize ZFYVE1, ATG9, LC3B, ATG16L1, ATG5, STX17, RAB7 and LAMP1, which represent different stages process. It required for as phenotype was significantly decreased in EVA1A- silenced cells Eva1a KO MEFs. EVA1A-induced autophagy independent BECN1-PIK3C3 (phosphatidylinositol 3-kinase, catalytic subunit type 3) complex but requires ATG7 activity ATG12–ATG5/ATG16L1 complex. Here, present molecular mechanism interacts WD repeats ATG16L1 through its C-terminal promotes recruitment enhances autophagosome. We also found both apoptotic mechanisms contributed cell death while inhibition apoptosis attenuated death. Overall, findings provide comprehensive view our understanding pathways involved role programmed