RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their membrane recruitment.
RILP is emerging as a key regulator of late endocytic pathway by functioning as a downstream effector of activated Rab7 and Rab34, while ESCRT-I-->ESCRT-II-->ESCRT-III machinery acts in sorting proteins to the multivesicular body (MVB) initiated at the early/sorting endosome. We show here that the early machinery is integrated with the ... late machinery through a novel regulatory loop in which RILP interacts with VPS22 and VPS36 of ESCRT-II to mediate their membrane recruitment. The N-terminal and C-terminal half of RILP mediate interaction with VPS22 and VPS36, respectively. Overexpression of RILP leads to enlarged and clustered MVBs marked by lysobisphosphatidic acid (LBPA). In addition, RILP or its C-terminal fragment causes a retardation of sorting internalized EGF to the degradation route at the level of sorting endosomes marked by EEA1. We propose that RILP-->ESCRT-II serves as a regulatory/feedback loop to govern the coordination of early and late parts of the endocytic pathway.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Binding Sites, Cytoplasm, Endocytosis, Endosomes, Epidermal Growth Factor, HeLa Cells, Humans, Intracellular Membranes
Adaptor Proteins, Signal Transducing, Binding Sites, Cytoplasm, Endocytosis, Endosomes, Epidermal Growth Factor, HeLa Cells, Humans, Intracellular Membranes
Biochem. Biophys. Res. Commun.
Date: Nov. 17, 2006
PubMed ID: 17010938
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