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Publication - Dr Chris Danson

    SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome

    Citation

    Danson, C, Brown, E, Hemmings, OJ, McGough, IJ, Yarwood, S, Heesom, KJ, Carlton, JG, Martin-Serrano, J, May, MT, Verkade, P & Cullen, PJ, 2013, ‘SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome’. Journal of Cell Science, vol 126., pp. 4885-4899

    Abstract

    Sorting nexins (SNXs) are key regulators of the endosomal network. In designing an RNAi-mediated loss-of-function screen, we establish that of thirty human SNXs only SNX3, SNX5, SNX9, SNX15 and SNX21 appear to regulate EGF receptor degradative sorting. Suppression of SNX15 results in a delay in receptor degradation arising from a defect in movement of newly internalised EGF receptor-labelled vesicles into early endosomes. Besides a PtdIns(3)P- and PX domain-dependent association to early endosomes, SNX15 also associates with clathrin-coated pits and clathrin-coated vesicles via direct binding to clathrin through a non-canonical clathrin-binding box. From live cell imaging, the activated EGF receptor enters distinct sub-populations of SNX15- and APPL1-labelled peripheral endocytic vesicles, which do not undergo heterotypic fusion. The SNX15-decorated receptor-containing sub-population does however undergo direct fusion with the Rab5-labelled early endosome. Our data is consistent with a model in which the EGF receptor enters the early endosome following clathrin-mediated endocytosis through at least two parallel pathways: maturation via an APPL1-intermediate compartment and an alternative more direct fusion between SNX15 decorated endocytic vesicles and the Rab5-positive early endosome.

    Full details in the University publications repository