A novel mode of Capping Protein-regulation by Twinfilin
- Brandeis University, United States
- Washington University in St Louis, United States
Abstract
Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first 'pro-capping' ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle.
Data availability
All datasets associated with this article are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institutes of Health (R01 GM063691)
- Bruce L Goode
Defense Threat Reduction Agency (HDTRA1-16-1-0033)
- Gaya K Amarasinghe
National Institutes of Health (R35 GM118171)
- John A Cooper
National Science Foundation (MRSEC DMR-1420382)
- Bruce L Goode
National Institutes of Health (P01 AI120943)
- Gaya K Amarasinghe
National Institutes of Health (R01 AI123926)
- Gaya K Amarasinghe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anna Akhmanova, Utrecht University, Netherlands
Publication history
- Received: August 21, 2018
- Accepted: October 22, 2018
- Accepted Manuscript published: October 23, 2018 (version 1)
- Version of Record published: November 21, 2018 (version 2)
Copyright
© 2018, Johnston et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A novel mode of Capping Protein-regulation by Twinfilin
eLife 7:e41313.
https://doi.org/10.7554/eLife.41313
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