Structure and dynamics of FCHo2 docking on membranes

F. El Alaoui , I. Casuso , D. Sanchez-Fuentes , C. André-Arpin , R. Rathar , V. Baecker , A. Castro , T. Lorca , J. Viaud , S. Vassilopoulos , A. Carretero-Genevrier , Laura Picas (1, 2)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 UM - Université de Montpellier

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 2 ) 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 remains elusive. Here, we show the molecular dynamics of FCHo2 self-assembly on membranes by combining bottom-up synthetic approaches on in vitro and cellular membranes. Our results indicate that PI(4,5)P 2 domains assist FCHo2 docking at specific membrane regions, where it self-assembles into ring-like shape protein patches. We show that binding of FCHo2 on cellular membranes promotes PI(4,5)P 2 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 2 -interacting proteins at endocytic sites.

Domaines: Sciences du Vivant [q-bio]

F. El Alaoui, I. Casuso, D. Sanchez-Fuentes, C. André-Arpin, R. Rathar, et al.. Structure and dynamics of FCHo2 docking on membranes. 2021. ⟨hal-03429469⟩