Multivalency in endocytic accessory proteins orchestrates membrane shape transitions

Multivalent SH3/PRM interactions between endophilin and lamellipodin form membrane-associated condensates that strongly suppress endophilin-mediated membrane tubulation in vitro.

• Why it matters: It was unclear how SH3/PRM-driven biomolecular condensation functionally impacts membrane remodeling during fast endophilin-mediated endocytosis.
• What they did: Using purified recombinant proteins, giant unilamellar vesicles, quantitative fluorescence microscopy, and in vitro phase separation assays, the study tested condensate regulation by competitive disruption with PP19 and by PRM valency constructs.
• The result: PP19 rapidly dissolves condensates and restores curvature generation without changing endophilin’s intrinsic curvature activity; the mechanism is conserved across endophilin A1, A2, and A3, requiring multivalent PRM7 but not mono- or divalent PRM constructs.