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

Miyuki Sato, Ken Sato, Paul Fonarev, Chih Jen Huang, Willisa Liou, Barth D. Grant

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


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 α-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.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalNature Cell Biology
Issue number6
StatePublished - Jun 2005

All Science Journal Classification (ASJC) codes

  • Cell Biology


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