RRC ID 51511
Author Liu H, Wang S, Hang W, Gao J, Zhang W, Cheng Z, Yang C, He J, Zhou J, Chen J, Shi A.
Title LET-413/Erbin acts as a RAB-5 effector to promote RAB-10 activation during endocytic recycling.
Journal J Cell Biol
Abstract RAB-10/Rab10 is a master regulator of endocytic recycling in epithelial cells. To better understand the regulation of RAB-10 activity, we sought to identify RAB-10(GDP)-interacting proteins. One novel RAB-10(GDP)-binding partner that we identified, LET-413, is the Caenorhabditis elegans homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the C. elegans intestine. We show that LET-413 is a RAB-5 effector and colocalizes with RAB-10 on endosomes, and the overlap of LET-413 with RAB-10 is RAB-5 dependent. Notably, LET-413 enhances the interaction of DENN-4 with RAB-10(GDP) and promotes DENN-4 guanine nucleotide exchange factor activity toward RAB-10. Loss of LET-413 leads to cytosolic dispersion of the RAB-10 effectors TBC-2 and CNT-1. Finally, we demonstrate that the loss of RAB-10 or LET-413 results in abnormal overextensions of lateral membrane. Hence, our studies indicate that LET-413 is required for DENN-4-mediated RAB-10 activation, and the LET-413-assisted RAB-5 to RAB-10 cascade contributes to the integrity of C. elegans intestinal epithelia.
Volume 217(1)
Pages 299-314
Published 2018-1-2
DOI 10.1083/jcb.201705136
PII jcb.201705136
PMID 29079669
PMC PMC5748983
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line, Tumor Cell Polarity / physiology Endocytosis / physiology Enzyme Activation Epithelial Cells / metabolism GTPase-Activating Proteins / metabolism Guanine Nucleotide Exchange Factors / metabolism Guanylate Kinases / genetics HeLa Cells Humans Intestinal Mucosa / physiology* Protein Transport / physiology Vesicular Transport Proteins / metabolism* rab GTP-Binding Proteins / metabolism*
IF 8.811
Times Cited 11
C.elegans tm1447 tm2523 tm2616