Structural organization and dynamics of FCHo2 docking on membranes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35044298.
- Also identified by DOI 10.7554/eLife.73156 and PMC identifier 8798043.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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)P<sub>2</sub>) 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)P<sub>2</sub> 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)P<sub>2</sub> 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)P<sub>2</sub>-interacting proteins at endocytic sites.
Medical subject headings
- Cell Membrane
- Clathrin
- Endocytosis
- Fatty Acid-Binding Proteins