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Cargo induces retromer-mediated membrane remodeling on membranes
Abstract
Endosomes serve as a central sorting station of lipids and proteins that arrive via vesicular carrier from the plasma membrane and the Golgi complex. At the endosome, retromer complexes sort selected receptors and membrane proteins into tubules or vesicles that bud off the endosome. The mature endosome finally fuses with the lysosome. Retromer complexes consist of a cargo selection complex (CSC) and a membrane remodeling part (sorting nexin [SNX]-Bin/amphiphysin/Rvs [BAR], or Snx3 in yeast) and different assemblies of retromer mediate recycling of different cargoes. Due to this complexity, the exact order of events that results in carrier formation is not yet understood. Here, we reconstituted this process on giant unilamellar vesicles together with purified retromer complexes from yeast and selected cargoes. Our data reveal that the membrane remodeling activity of both Snx3 and the SNX-BAR complex is strongly reduced at low concentrations, which can be reactivated by CSC. At even lower concentrations, these complexes still associate with membranes, but only remodel membranes in the presence of their specific cargoes. Our data thus favor a simple model, where cargo functions as a specific trigger of retromer-mediated sorting on endosomes.
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Various sorting nexin proteins, such as SNX27, SNX32, SNX1-SNX6, and SNX1-SNX5, are autoinhibited in the basal state, with cargo binding enhancing their association with Retromer or membranes.
“Interestingly, various sorting nexin proteins, such as SNX2729, SNX326,39, SNX1-SNX628, and SNX1-SNX540, operate similarly, being autoinhibited in the basal state, with cargo binding enhancing their association with Retromer or membranes.”
From Structural basis for Retriever-SNX17 assembly and endosomal sorting (2024) · cites this paper as [39]
The Results (‘Cargo can be limiting for SNX-retromer membrane remodeling activity’; page unavailable) show that Vps10 cargo induces SNX-BAR retromer tubulation under conditions where it otherwise does not occur. The Discussion proposes that cargo may promote assembly of SNX-BAR and retromer complexes, but does not establish basal autoinhibition or the claimed mechanism across SNX27, SNX32, SNX1–SNX6, and SNX1–SNX5. (LLM, conf=0.86)
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Retromer: A Master Conductor of Endosome Sorting
Burd, C., & Cullen, P. J. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016774 · Cited by 435
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Structural basis for Retriever-SNX17 assembly and endosomal sorting
Singla, A., Boesch, D. J., Fung, H. Y. J., Ngoka, C., Enriquez, A. S., Song, R., Kramer, D. A., Han, Y., Banarer, E., Lemoff, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54583-6 · Cited by 23
Retromer dysfunction at the nexus of tauopathies
Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-020-00727-2 · Cited by 16
Metadata
- Authors
- Purushothaman, L. K., & Ungermann, C.
- Venue
- Molecular Biology of the Cell
- Published
- 2018-11
- Volume
- 29
- Issue
- 22
- Pages
- 2709-2719
- ISSN
- 1059-1524
- 1939-4586
- PMC
- PMC6249844
- Cited by
- 35
- References
- 1
- Language
- en
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