ANKRD50 is an essential component of the endosomal SNX27-retromer-WASH supercomplex that supports endosome-to-plasma-membrane recycling of transmembrane cargo PMID:27909246. It was first identified as a VPS35-interacting protein, with its depletion causing trafficking defects of retromer-dependent cargo PMID:25278552. ANKRD50 simultaneously engages multiple parts of the SNX27-retromer-WASH machinery through direct and cooperative interactions, and its loss phenocopies suppression of SNX27, retromer, or WASH components, impairing cell-surface recycling of transmembrane proteins including the nutrient transporters GLUT1/SLC2A1 and SLC1A4 PMID:27909246. The Parkinson's disease-causing VPS35 D620N mutation perturbs retromer's association with ANKRD50 PMID:27909246. Beyond these interaction and cargo-recycling findings, no further mechanistic detail has been characterized in the available corpus.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2014 | Medium | ANKRD50 was identified as a novel interacting protein of VPS35, the core retromer component, via quantitative proteomics of the human VPS35 interactome. Depletion of ANKRD50 resulted in trafficking defects of retromer-dependent cargo, indicating a functional role in endosome-to-plasma-membrane sorting. | PMID:25278552 | Journal of cell science |
| 2016 | High | ANKRD50 was established as an essential component of the SNX27-retromer-WASH supercomplex. Mechanistically, ANKRD50 simultaneously engages multiple parts of the SNX27-retromer-WASH machinery through direct and cooperative interactions. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied loss of endosome-to-cell-surface recycling of multiple transmembrane proteins (including GLUT1/SLC2A1 and SLC1A4) seen upon suppression of SNX27, retromer, or WASH complex components. The Parkinson's disease-causing VPS35 D620N mutation also perturbs retromer's association with ANKRD50. | PMID:27909246 | Journal of cell science |