Abstract
Endosomal recycling of transmembrane proteins requires sequence-dependent recognition of motifs present within their intracellular cytosolic domains. In this study, we have reexamined the role of retromer in the sequence-dependent endosome-to–trans-Golgi network (TGN) transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)–Bin, Amphiphysin, and Rvs (BAR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport. The retromer-linked SNX-BAR proteins comprise heterodimeric combinations of SNX1 or SNX2 with SNX5 or SNX6 and serve to regulate the biogenesis of tubular endosomal sorting profiles. We establish that SNX5 and SNX6 associate with the CI-MPR through recognition of a specific WLM endosome-to-TGN sorting motif. From validating the CI-MPR dependency of SNX1/2–SNX5/6 tubular profile formation, we provide a mechanism for coupling sequence-dependent cargo recognition with the biogenesis of tubular profiles required for endosome-to-TGN transport. Therefore, the data presented in this study reappraise retromer’s role in CI-MPR transport.
Original language | English |
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Pages (from-to) | 3695-3712 |
Number of pages | 18 |
Journal | Journal of Cell Biology |
Volume | 216 |
Issue number | 11 |
Early online date | 21 Sep 2017 |
DOIs | |
Publication status | E-pub ahead of print - 21 Sep 2017 |
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Professor Pete J Cullen
- Fundamental Bioscience
- School of Biochemistry - Professor of Biochemistry (Royal Society Wolfson Research Merit Award Holder)
- Dynamic Cell Biology
- Bristol Neuroscience
Person: Academic , Member, Group lead