Publication

Article Metrics

Citations


Online attention

A flat BAR Protein promotes actin polymerization at the base of clathrin-coated pits

DOI: 10.1016/j.cell.2018.05.020 DOI Help

Authors: Leonardo Almeida-souza (MRC Laboratory of Molecular Biology) , Rene A. W. Frank (MRC Laboratory of Molecular Biology) , Javier Garcia-nafria (MRC Laboratory of Molecular Biology) , Adeline Colussi (MRC Laboratory of Molecular Biology) , Nushan Gunawardana (MRC Laboratory of Molecular Biology) , Christopher M. Johnson (MRC Laboratory of Molecular Biology) , Minmin Yu (MRC Laboratory of Molecular Biology) , Gillian Howard (MRC Laboratory of Molecular Biology) , Byron Andrews (MRC Laboratory of Molecular Biology) , Yvonne Vallis (MRC Laboratory of Molecular Biology) , Harvey T. Mcmahon (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell

State: Published (Approved)
Published: June 2018
Diamond Proposal Number(s): 11235

Open Access Open Access

Abstract: Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. FCHSD2 deletion leads to decreased ligand uptake caused by slowed pit maturation. FCHSD2 is recruited to endocytic pits by the scaffold protein intersectin via an unusual SH3-SH3 interaction. Here, its flat F-BAR domain binds to the planar region of the plasma membrane surrounding the developing pit forming an annulus. When bound to the membrane, FCHSD2 activates actin polymerization by a mechanism that combines oligomerization and recruitment of N-WASP to PI(4,5)P2, thus promoting pit maturation. Our data therefore describe a molecular mechanism for linking spatiotemporally the plasma membrane to a force-generating actin platform guiding endocytic vesicle maturation.

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Documents:
S0092-8674(18)30597-X.pdf