Clathrin-mediated endocytosis (CME) is a central trafficking pathway in eukaryotic cells regulated by phosphoinositides. The plasma membrane phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an instrumental role in driving CME initiation. The F-BAR domain only protein 1 and 2 complex (FCHo1/2) is among the early proteins that reach the plasma membrane, but the exact mechanisms triggering its recruitment remain elusive. Here, we show the molecular dynamics of FCHo2 self-assembly on membranes by combining minimal reconstituted in vitro and cellular systems. Our results indicate that PI(4,5)P2 domains assist FCHo2 docking at specific membrane regions, where it self-assembles into ring-like shape protein patches. We show that the binding of FCHo2 on cellular membranes promotes PI(4,5)P2 clustering at the boundary of cargo receptors and that this accumulation enhances clathrin assembly. Thus, our results provide a mechanistic framework that could explain the recruitment of early PI(4,5)P2-interacting proteins at endocytic sites.
All data generated or analyzed during this study are included in the manuscript and supporting file. Datasets are available at Dryad, doi:10.5061/dryad.n8pk0p2wp
Data from: Structural organization and dynamics of FCHo2 docking on membranesDryad Digital Repository, doi:10.5061/dryad.n8pk0p2wp.
- Volker Baecker
- Laura Picas
- Laura Picas
- Adrien Carretero-Genevrier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States
© 2022, El Alaoui et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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