Endosomes are protein sorting stations, where multiple membrane coats form tubulovesicular carriers exporting proteins to the Golgi, the plasma membrane, or endo-lysosomal compartments. Distinct classes of sorting nexins are assumed to form distinct homogeneous coats that define the endosomal sorting routes and their cargos. Snx3 and the SNX-BAR proteins Vps5-Vps17 belong to different sorting-nexin classes. They can form homogeneous retromer-dependent coats that differ in structure and in their modes of membrane association and cargo recognition. Here, we describe the formation of hybrid coats between purified SNX-BARs, Snx3, and their cargos. Hybrid coats assemble at variable subunit ratios and diameters and show greater membrane-scaffolding activity than homogeneous coats. In vivo, Snx3 and SNX-BARs co-localise and mutually impact the sorting of their respective cargos. Although simultaneous binding of Snx3- and SNX-BARs to Retromer is sterically prohibited, hybrid coats incorporate both SNXs in a common complex, probably linked by retromer oligomerisation. We hence propose that SNX-BARs and Snx3 form retromer-mediated hybrid coats in novel, stoichiometrically adaptable configurations that allow the adjustment of endosomal carriers for transporting varying ratios of cargo.

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Journal Article

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Gopaldass N, Roy Chowdhury S, Alves AC, Michaillat Mayer L, Comte-Misérez V, Mayer A

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