LET-413/Erbin Acts As a RAB-5 Effector to Promote RAB-10 Activation During Endocytic Recycling

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2017 Oct 29

PMID 29079669

Citations 22

Authors

Hang Liu

Shimin Wang

Weijian Hang

Jinghu Gao

Wenjuan Zhang

Zihang Cheng

Chao Yang

Jun He

Jie Zhou

Juan Chen

Anbing Shi

Affiliations

Soon will be listed here.

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 homologue of Scrib/Erbin. Here, we focus on the mechanistic role of LET-413 in the regulation of RAB-10 within the 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 intestinal epithelia.

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