RAB-10-GTPase -mediated regulation of endosomal phosphatidylinositol-4,5- bisphosphate

Anbing Shi, Ou Liu, Sabine Koenig, Riju Banerjee, Carlos Chih Hsiung Chen, Stefan Eimer, Barth D. Grant

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Caenorhabditis elegans RAB-10 and mammalian Rab10 are key regulators of endocytic recycling, especially in the basolateral recycling pathways of polarized epithelial cells. To understand better how RAB-10 contributes to recycling endosome function, we sought to identify RAB-10 effectors. One RAB-10-binding partner that we identified, CNT-1, is the only C. elegans homolog of the mammalian Arf6 GTPase-activating proteins ACAP1 and ACAP2. Arf6 is known to regulate endosome-to-plasma membrane transport, in part through activation of type I phophatidylinositol-4-phosphate 5 kinase. Here we show that CNT-1 binds to RAB-10 through its C-terminal ankyrin repeats and colocalizes with RAB-10 and ARF-6 on recycling endosomes in vivo. Furthermore, we find that RAB-10 is required for the recruitment of CNT-1 to endosomal membranes in the intestinal epithelium. Consistent with negative regulation of ARF-6 by RAB-10 and CNT-1, we found overaccumulation of endosomal phosphatidylinositol-4,5- bisphosphate [PI(4,5)P2] in cnt-1 and rab-10 mutants and reduced endosomal PI(4,5)P2 levels in arf-6 mutants. These mutants produced similar effects on endosomal recruitment of the PI(4,5)P2-dependent membrane-bending proteins RME-1/Ehd and SDPN-1/Syndapin/ Pacsin and resulted in endosomal trapping of specific recycling cargo. Our studies identify a RAB-10- to-ARF-6 regulatory loop required to regulate endosomal PI(4,5)P2, a key phosphoinositide in membrane traffic.

Original languageEnglish (US)
Pages (from-to)E2306-E2315
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
StatePublished - Aug 28 2012

All Science Journal Classification (ASJC) codes

  • General


  • Clathrin
  • Membrane lipid

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