Open AccessRAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes
Author(s) -
Peixiang Wang,
Huan Liu,
Yu Wang,
Ou Liu,
Jing Zhang,
Adenrele M. Gleason,
Zihao Yang,
Hui Wang,
Anbing Shi,
Barth D. Grant
Publication year - 2016
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006093
Subject(s) - rab , endosome , microbiology and biotechnology , biology , endocytic cycle , gtpase , actin , pleckstrin homology domain , actin cytoskeleton , cytoskeleton , endocytosis , biochemistry , phosphorylation , cell , intracellular
EHBP-1 (Ehbp1) is a conserved regulator of endocytic recycling, acting as an effector of small GTPases including RAB-10 (Rab10). Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] enriched membranes through an N-terminal C2-like (NT-C2) domain, and define residues within the NT-C2 domain that mediate membrane interaction. Furthermore, our results indicate that the EHBP-1 central calponin homology (CH) domain binds to actin microfilaments in a reaction that is stimulated by RAB-10(GTP). Loss of any aspect of this RAB-10/EHBP-1 system in the C . elegans intestinal epithelium leads to retention of basolateral recycling cargo in endosomes that have lost their normal tubular endosomal network (TEN) organization. We propose a mechanism whereby RAB-10 promotes the ability of endosome-bound EHBP-1 to also bind to the actin cytoskeleton, thereby promoting endosomal tubulation.