Structural organization and dynamics of FCHo2 docking on membranes

eLife

Thierry Lorca¹  Anna Castro¹  Julien Viaud²  David Sanchez-Fuentes³  Raissa Rathar³  Adrian Carretero-Genevrier³  Laura Picas⁴  Fatima El Alaoui⁴  Charlotte Arpin-Andre⁴  Volker Baecker⁵  Stéphane Vassilopoulos⁶  Ignacio Casuso⁷ 

[1]Centre de Biologie Cellulaire de Montpellier (CRBM), CNRS UMR UMR 5237, Université de Montpellier, Montpellier, France

[2]INSERM UMR1297, Institute of Metabolic and Cardiovascular Diseases (I2MC), University of Toulouse, Paul Sabatier University, Toulouse, France

[3]Institut d'Électronique et des Systèmes (IES), CNRS UMR 5214, Université de Montpellier, Montpellier, France

[4]Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS UMR 9004, Université de Montpellier, Montpellier, France

[5]Montpellier Ressources Imagerie, BioCampus Montpellier, CNRS, INSERM, Université de Montpellier, Montpellier, France

[6]Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, Paris, France

[7]U1067 INSERM, Aix-Marseille Université, Marseille, France

关键词: membranes;    phosphoinositides;    BAR proteins;    endocytosis;    AFM;    fluorescence microscopy;    Other;   

DOI  :  10.7554/eLife.73156

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY