RRC ID 4289
Author Sato M, Sato K, Liou W, Pant S, Harada A, Grant BD.
Title Regulation of endocytic recycling by C. elegans Rab35 and its regulator RME-4, a coated-pit protein.
Journal EMBO J.
Abstract Using Caenorhabditis elegans genetic screens, we identified receptor-mediated endocytosis (RME)-4 and RME-5/RAB-35 as important regulators of yolk endocytosis in vivo. In rme-4 and rab-35 mutants, yolk receptors do not accumulate on the plasma membrane as would be expected in an internalization mutant, rather the receptors are lost from cortical endosomes and accumulate in dispersed small vesicles, suggesting a defect in receptor recycling. Consistent with this, genetic tests indicate the RME-4 and RAB-35 function downstream of clathrin, upstream of RAB-7, and act synergistically with recycling regulators RAB-11 and RME-1. We find that RME-4 is a conserved DENN domain protein that binds to RAB-35 in its GDP-loaded conformation. GFP-RME-4 also physically interacts with AP-2, is enriched on clathrin-coated pits, and requires clathrin but not RAB-5 for cortical association. GFP-RAB-35 localizes to the plasma membrane and early endocytic compartments but is lost from endosomes in rme-4 mutants. We propose that RME-4 functions on coated pits and/or vesicles to recruit RAB-35, which in turn functions in the endosome to promote receptor recycling.
Volume 27(8)
Pages 1183-96
Published 2008-4-23
DOI 10.1038/emboj.2008.54
PII emboj200854
PMID 18354496
PMC PMC2367398
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Carrier Proteins / genetics Carrier Proteins / physiology* Cell Membrane / chemistry Cell Membrane / metabolism Cell Membrane / physiology Coated Pits, Cell-Membrane / metabolism Coated Pits, Cell-Membrane / physiology* Egg Yolk / metabolism Endocytosis / physiology* Endosomes / metabolism Endosomes / physiology Membrane Proteins / genetics Membrane Proteins / physiology* Molecular Sequence Data rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / physiology*
IF 10.557
Times Cited 87
C.elegans rme-4(tm1865)