Structural organization and dynamics of FCHo2 docking on membranes

Elife. 2022 Jan 19;11:e73156. doi: 10.7554/eLife.73156.


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-shaped 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.

Keywords: AFM; BAR proteins; endocytosis; fluorescence microscopy; membranes; molecular biophysics; phosphoinositides; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Clathrin / metabolism*
  • Endocytosis / genetics*
  • Fatty Acid-Binding Proteins / genetics*
  • Fatty Acid-Binding Proteins / metabolism
  • Humans


  • Clathrin
  • FCHO2 protein, human
  • Fatty Acid-Binding Proteins

Associated data

  • Dryad/10.5061/dryad.n8pk0p2wp

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.