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PMID: 15895077 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit.

Nature cell biology ·Vol. 7 ·No. 6 ·2005-06-00 ·Pages 559-69

Sato M, Sato K, Fonarev P, Huang CJ, Liou W, Grant BD

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.

MeSH Terms
Adaptor Protein Complex alpha Subunits/metabolism Animals Caenorhabditis elegans/genetics,metabolism,ultrastructure Caenorhabditis elegans Proteins/genetics,isolation & purification,metabolism Cell Membrane/metabolism,ultrastructure Clathrin-Coated Vesicles/metabolism,ultrastructure Endocytosis/physiology Endosomes/metabolism Membrane Proteins/genetics,isolation & purification,metabolism Microscopy, Electron, Transmission Molecular Sequence Data Mutation Phenotype Protein Binding/physiology Protein Transport/physiology Recombinant Fusion Proteins/genetics,metabolism Transport Vesicles/metabolism rab5 GTP-Binding Proteins/genetics,metabolism
Chemicals
Adaptor Protein Complex alpha Subunits Caenorhabditis elegans Proteins Membrane Proteins RME-6 protein, C elegans Recombinant Fusion Proteins rab5 GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sato Miyuki
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Sato Ken
Fonarev Paul
Huang Chih-Jen
Liou Willisa
Grant Barth D
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1465-7392
DOI
10.1038/ncb1261
Published
2005-06-00
Epub
2005-00-15
Pages
559-69
Language
English
Region
England
NLM ID
100890575
PMCID
PMC1398054
Subset
IM
Grants
NIGMS NIH HHS · R01 GM067237 · United States
NIGMS NIH HHS · GM67237 · United States
Databases
GENBANK
AY750054
Corrections
CommentIn
PMID: 15928700
External Links
PubMed source DOI: 10.1038/ncb1261 PMC Full Text View journal details
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