Retromer oligomerization drives SNX‐BAR coat assembly and membrane constriction

Abstract: Proteins exit from endosomes through tubular carriers coated by retromer, a complex that impacts cellular signaling, lysosomal biogenesis and numerous diseases. The coat must overcome membrane tension to form tubules. We explored the dynamics and driving force of this process by reconstituting coat formation with yeast retromer and the BAR‐domain sorting nexins Vps5 and Vps17 on oriented synthetic lipid tubules. This coat oligomerizes bidirectionally, forming a static tubular structure that does not exchange subunits. High concentrations of sorting nexins alone constrict membrane tubes to an invariant radius of 19 nm. At lower concentrations, oligomers of retromer must bind and interconnect the sorting nexins to drive constriction. Constricting less curved membranes into tubes, which requires more energy, coincides with an increased surface density of retromer on the sorting nexin layer. Retromer‐mediated crosslinking of sorting nexins at variable densities may thus tune the energy that the coat can generate to deform the membrane. In line with this, genetic ablation of retromer oligomerization impairs endosomal protein exit in yeast and human cells.

Objekt anzeigen

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Retromer oligomerization drives SNX‐BAR coat assembly and membrane constriction ; volume:42 ; number:2 ; year:2023 ; extent:29 ; The EMBO journal / European Molecular Biology Organization ; 42, Heft 2 (2023) (gesamt 29)

Beteiligte, Orts- und Zeitangaben

• Urheber: Gopaldass, Navin ; De Leo, Maria Giovanna ; Courtellemont, Thibault ; Mercier, Vincent ; Bissig, Christin ; Roux, Aurélien ; Mayer, Andreas

Weitere Informationen

• DOI: 10.15252/embj.2022112287
• URN: urn:nbn:de:101:1-2023011614245693616559
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.