Projects per year
The retromer complex acts as a scaffold for endosomal protein complexes that sort integral membrane proteins to various cellular destinations. The retromer complex is a heterotrimer of VPS29, VPS35, and VPS26. Two of these paralogues, VPS26A and VPS26B, are expressed in humans. Retromer dysfunction is associated with neurodegenerative disease, and recently, three VPS26A mutations (p.K93E, p.M112V, and p.K297X) were discovered to be associated with atypical parkinsonism. Here, we apply quantitative proteomics to provide a detailed description of the retromer interactome. By establishing a comparative proteomic methodology, we identify how this interactome is perturbed in atypical parkinsonism-associated VPS26A mutants. In particular, we describe a selective defect in the association of VPS26A (p.K297X) with the SNX27 cargo adaptor. By showing how a retromer mutant leads to altered endosomal sorting of specific PDZ ligand-containing cargo proteins, we reveal a new mechanism for perturbed endosomal cargo sorting in atypical parkinsonism.
|Number of pages||11|
|Journal||Journal of Cell Biology|
|Publication status||Published - 15 Aug 2016|
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- 1 Finished
Analysing the cell biology of Parkinson's Disease-linked missense mutation in the retromer VPS35 subunit.
1/10/13 → 30/09/16
Wolfson Bioimaging Facility
Mark Jepson (Manager)Faculty of Life Sciences
Professor Pete J Cullen
- School of Biochemistry - Royal Society Noreen Murray Research Professor
- Fundamental Bioscience
- Dynamic Cell Biology
- Bristol Neuroscience
Person: Academic , Member, Group lead