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

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

Author information

1
Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA.
2
Departments of Cell Biology and Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
3
Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
4
Department of Neuroscience, Karolinska Institutet, von Eulers väg 3, 171 77 Stockholm, Sweden.
5
Martin Fisher School of Physics, Brandeis University, Waltham, MA 02453, USA.
6
Department of Bioengineering, Faculty of Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia.
7
Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: arodal@brandeis.edu.

Abstract

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

PMID:
26686642
PMCID:
PMC4790443
DOI:
10.1016/j.celrep.2015.11.044
[Indexed for MEDLINE]
Free PMC Article

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