Liquid-like protein interactions catalyse assembly of endocytic vesicles

Kasey J. Day, Grace Kago, Liping Wang, J. Blair Richter, Carl C. Hayden, Eileen M. Lafer, Jeanne C. Stachowiak

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


During clathrin-mediated endocytosis, dozens of proteins assemble into an interconnected network at the plasma membrane. As initiators of endocytosis, Eps15 and Fcho1/2 concentrate downstream components, while permitting dynamic rearrangement within the budding vesicle. How do initiator proteins meet these competing demands? Here we show that Eps15 and Fcho1/2 rely on weak, liquid-like interactions to catalyse endocytosis. In vitro, these weak interactions promote the assembly of protein droplets with liquid-like properties. To probe the physiological role of these liquid-like networks, we tuned the strength of initiator protein assembly in real time using light-inducible oligomerization of Eps15. Low light levels drove liquid-like assemblies, restoring normal rates of endocytosis in mammalian Eps15-knockout cells. By contrast, initiator proteins formed solid-like assemblies upon exposure to higher light levels, which stalled vesicle budding, probably owing to insufficient molecular rearrangement. These findings suggest that liquid-like assembly of initiator proteins provides an optimal catalytic platform for endocytosis.

Original languageEnglish (US)
Pages (from-to)366-376
Number of pages11
JournalNature Cell Biology
Issue number4
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Cell Biology


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