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

Charlotte F. Kelley, Emily M. Messelaar, Tania L. Eskin, Shiyu Wang, Kangkang Song, Kalanit Vishnia, Agata N. Becalska, Oleg Shupliakov, Michael F. Hagan, Dganit Danino, Olga S. Sokolova, Daniela Nicastro, Avital A. Rodal

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2597-2609
Number of pages13
JournalCell Reports
Issue number11
StatePublished - Dec 22 2015


  • Drosophila
  • F-BAR domain
  • Membrane
  • Nwk
  • PI(4,5)P
  • SH3 domain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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