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Resources » Paper

Shi A et al. (2012) Proc Natl Acad Sci U S A "RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate."

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  • Comments on Shi A et al. (2012) Proc Natl Acad Sci U S A "RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate." (0)

  • Overview

    PMID:
    22869721
    DOI:
    10.1073/pnas.1205278109
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00041380

    Shi A, Liu O, Koenig S, Banerjee R, Chen CC, Eimer S, & Grant BD (2012). RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate. Proc Natl Acad Sci U S A, 109, E2306-15. doi:10.1073/pnas.1205278109

    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.


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