title: RILP interacts with HOPS complex via VPS41 subunit to regulate endocytic trafficking.
abstract: The HOPS complex serves as a tethering complex with GEF activity for Ypt7p in yeast to regulate late endosomal membrane maturation. While the role of HOPS complex is well established in yeast cells, its functional and mechanistic aspects in mammalian cells are less well defined. In this study, we report that RILP, a downstream effector of Rab7, interacts with HOPS complex and recruits HOPS subunits to the late endosomal compartment. Structurally, the amino-terminal portion of RILP interacts with HOPS complex. Unexpectedly, this interaction is independent of Rab7. VPS41 subunit of HOPS complex was defined to be the major partner for interacting with RILP. The carboxyl-terminal region of VPS41 was mapped to be responsible for the interaction. Functionally, either depletion of VPS41 by shRNA or overexpression of VPS41 C-terminal half retarded EGF-induced degradation of EGFR. These results suggest that interaction of RILP with HOPS complex via VPS41 plays a role in endocytic trafficking of EGFR.
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Xiaosi
authors.initials: X
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Shicong
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yun
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Health Sciences, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-Ku, Tokyo 113-8519, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akazawa
authors.affiliation: 1] School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005 [2] Institute of Molecular and Cell Biology, A STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.affiliation: School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China, 361005.
authors.forename: Tuanlao
authors.initials: T
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D022161:Transport Vesicles / Q000378:metabolism* / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009687:Nuclear Proteins; C423317:RILP protein, human; C549959:VPS41 protein, human; D033921:Vesicular Transport Proteins; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors