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Structural organization and dynamics of FCHo2 docking on membranes.

Authors :: El Alaoui F
Casuso I
Sanchez-Fuentes D
Arpin-Andre C
Rathar R
Baecker V
Castro A
Lorca T
Viaud J
Vassilopoulos S
Carretero-Genevrier A
Picas L
Source :: ELife [Elife] 2022 Jan 19; Vol. 11. Date of Electronic Publication: 2022 Jan 19.
Publication Year :: 2022
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 <subscript>2</subscript> ) 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 <subscript>2</subscript> 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 <subscript>2</subscript> 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 <subscript>2</subscript> -interacting proteins at endocytic sites.<br />Competing Interests: FE, IC, DS, CA, RR, VB, AC, TL, JV, SV, AC, LP No competing interests declared<br /> (© 2022, El Alaoui et al.)