RRC ID 437
Author Sato M, Sato K, Fonarev P, Huang CJ, Liou W, Grant BD.
Title Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit.
Journal Nat Cell Biol
Abstract Here we identify a new regulator of endocytosis called RME-6. RME-6 is evolutionarily conserved among metazoans and contains Ras-GAP (GTPase-activating protein)-like and Vps9 domains. Consistent with the known catalytic function of Vps9 domains in Rab5 GDP/GTP exchange, we found that RME-6 binds specifically to Caenorhabditis elegans RAB-5 in the GDP-bound conformation, and rme-6 mutants have phenotypes that indicate low RAB-5 activity. However, unlike other Rab5-associated proteins, a rescuing green fluorescent protein (GFP)-RME-6 fusion protein primarily localizes to clathrin-coated pits, physically interacts with alpha-adaptin, a clathrin adaptor protein, and requires clathrin to achieve its cortical localization. In rme-6 mutants, transport from the plasma membrane to endosomes is defective, and small 110-nm endocytic vesicles accumulate just below the plasma membrane. These results suggest a mechanism for the activation of Rab5 in clathrin-coated pits or clathrin-coated vesicles that is essential for the delivery of endocytic cargo to early endosomes.
Volume 7(6)
Pages 559-69
Published 2005-6-1
DOI 10.1038/ncb1261
PII ncb1261
PMID 15895077
PMC PMC1398054
MeSH Adaptor Protein Complex alpha Subunits / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / isolation & purification Caenorhabditis elegans Proteins / metabolism* Cell Membrane / metabolism* Cell Membrane / ultrastructure Clathrin-Coated Vesicles / metabolism* Clathrin-Coated Vesicles / ultrastructure Endocytosis / physiology* Endosomes / metabolism Membrane Proteins / genetics Membrane Proteins / isolation & purification Membrane Proteins / metabolism* Microscopy, Electron, Transmission Molecular Sequence Data Mutation Phenotype Protein Binding / physiology Protein Transport / physiology Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transport Vesicles / metabolism rab5 GTP-Binding Proteins / genetics rab5 GTP-Binding Proteins / metabolism*
IF 17.728
Times Cited 115
C.elegans tm1512