2. Academic Validation
  3. A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits

A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits

  • Cell. 2018 Jul 12;174(2):325-337.e14. doi: 10.1016/j.cell.2018.05.020.
Leonardo Almeida-Souza 1,  Rene A W Frank 2,  Javier García-Nafría 2,  Adeline Colussi 2,  Nushan Gunawardana 2,  Christopher M Johnson 2,  Minmin Yu 2,  Gillian Howard 2,  Byron Andrews 2,  Yvonne Vallis 2,  Harvey T McMahon 3
Affiliations

Affiliations

  • 1 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: lalmeida@mrc-lmb.cam.ac.uk.
  • 2 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
  • 3 MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: hmm@mrc-lmb.cam.ac.uk.
PMID: 29887380 DOI: 10.1016/j.cell.2018.05.020
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.

Keywords

ARP2/3; BAR domain; FCHSD2; N-WASP activation; Nervous Wreck; actin cytoskeleton; clathrin-mediated endocytosis; cytoskeletal forces; intersectin; membrane deformation.

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