テラワキ　セイゴウ   Seigo Terawaki   寺脇　正剛    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   特任講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins.
掲載誌名	正式名：Molecular cell 略　 称：Mol Cell ISSNコード：10974164/10972765
掲載区分	国外
巻・号・頁	57(1),pp.39-54
著者・共著者	McEwan David G, Popovic Doris, Gubas Andrea, Terawaki Seigo, Suzuki Hironori, Stadel Daniela, Coxon Fraser P, Miranda de Stegmann Diana, Bhogaraju Sagar, Maddi Karthik, Kirchof Anja, Gatti Evelina, Helfrich Miep H, Wakatsuki Soichi, Behrends Christian, Pierre Philippe, Dikic Ivan
発行年月	2015/01
概要	The lysosome is the final destination for degradation of endocytic cargo, plasma membrane constituents, and intracellular components sequestered by macroautophagy. Fusion of endosomes and autophagosomes with the lysosome depends on the GTPase Rab7 and the homotypic fusion and protein sorting (HOPS) complex, but adaptor proteins that link endocytic and autophagy pathways with lysosomes are poorly characterized. Herein, we show that Pleckstrin homology domain containing protein family member 1 (PLEKHM1) directly interacts with HOPS complex and contains a LC3-interacting region (LIR) that mediates its binding to autophagosomal membranes. Depletion of PLEKHM1 blocks lysosomal degradation of endocytic (EGFR) cargo and enhances presentation of MHC class I molecules. Moreover, genetic loss of PLEKHM1 impedes autophagy flux upon mTOR inhibition and PLEKHM1 regulates clearance of protein aggregates in an autophagy- and LIR-dependent manner. PLEKHM1 is thus a multivalent endocytic adaptor involved in the lysosome fusion events controlling selective and nonselective autophagy pathways.
DOI	10.1016/j.molcel.2014.11.006
PMID	25498145