Seigo Terawaki    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,    Position   Assistant Professor with Special Assignment
Article types	原著
Language	English
Peer review	Peer reviewed
Title	PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins.
Journal	Formal name：Molecular cell Abbreviation：Mol Cell ISSN code：10974164/10972765
Domestic / Foregin	Foregin
Volume, Issue, Page	57(1),pp.39-54
Author and coauthor	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
Publication date	2015/01
Summary	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