Membrane Charge Directs the Outcome of F-BAR Domain Lipid Binding and Autoregulation

Cell Rep. 2015 Dec 22;13(11):2597-2609. doi: 10.1016/j.celrep.2015.11.044. Epub 2015 Dec 10.


F-BAR domain proteins regulate and sense membrane curvature by interacting with negatively charged phospholipids and assembling into higher-order scaffolds. However, regulatory mechanisms controlling these interactions are poorly understood. Here, we show that Drosophila Nervous Wreck (Nwk) is autoregulated by a C-terminal SH3 domain module that interacts directly with its F-BAR domain. Surprisingly, this autoregulation does not mediate a simple "on-off" switch for membrane remodeling. Instead, the isolated Nwk F-BAR domain efficiently assembles into higher-order structures and deforms membranes only within a limited range of negative membrane charge, and autoregulation elevates this range. Thus, autoregulation could either reduce membrane binding or promote higher-order assembly, depending on local cellular membrane composition. Our findings uncover an unexpected mechanism by which lipid composition directs membrane remodeling.

Keywords: Drosophila; F-BAR domain; Nwk; PI(4,5)P(2); SH3 domain; membrane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Dimerization
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Larva / metabolism
  • Liposomes / metabolism
  • Microscopy, Confocal
  • Phospholipids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Static Electricity
  • src Homology Domains


  • Carrier Proteins
  • Drosophila Proteins
  • Liposomes
  • Phospholipids