Projects per year
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.
Original language | English |
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Pages (from-to) | 4885-4899 |
Journal | Journal of Cell Science |
Volume | 126 |
DOIs | |
Publication status | Published - 28 Aug 2013 |
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Dive into the research topics of 'SNX15 links clathrin endocytosis to the PtdIns(3)P early endosome independent of the APPL1 endosome'. Together they form a unique fingerprint.Projects
- 1 Finished
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Defining the mechanistic and functional details of an evolutionarily conserved non-canonical retromer pathway.
Cullen , P. J. (Principal Investigator)
12/12/11 → 12/12/14
Project: Research
Equipment
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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility