Calponin-homology domain mediated bending of membrane associated actin filaments
Abstract
Actin filaments are central to numerous biological processes in all domains of life. Driven by the interplay with molecular motors, actin binding and actin modulating proteins, the actin cytoskeleton exhibits a variety of geometries. This includes structures with a curved geometry such as axon-stabilizing actin rings, actin cages around mitochondria and the cytokinetic actomyosin ring, which are generally assumed to be formed by short linear filaments held together by actin cross-linkers. However, whether individual actin filaments in these structures could be curved and how they may assume a curved geometry remains unknown. Here, we show that 'curly', a region from the IQGAP family of proteins from three different organisms, comprising the actin-binding calponin-homology domain and a C-terminal unstructured domain, stabilizes individual actin filaments in a curved geometry when anchored to lipid membranes. Whereas F-actin is semi-flexible with a persistence length of ~10 mm, binding of mobile curly within lipid membranes generates actin filament arcs and full rings of high curvature with radii below 1 mm. Higher rates of fully formed actin rings are observed in the presence of the actin-binding coiled-coil protein tropomyosin and when actin is directly polymerized on lipid membranes decorated with curly. Strikingly, curly induced actin filament rings contract upon the addition of muscle myosin II filaments and expression of curly in mammalian cells leads to highly curved actin structures in the cytoskeleton. Taken together, our work identifies a new mechanism to generate highly curved actin filaments, which opens a range of possibilities to control actin filament geometries, that can be used, for example, in designing synthetic cytoskeletal structures.
Data availability
All data generated or analysed during the study are included in the manuscript and supporting files. Source data files for the actin curvature measurements (Figures 1-4) have been deposited and are freely availabe on Dyrad.
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Calponin-Homology Domain mediated bending of membrane associated actin filamentsDryad Digital Repository, doi: 10.5061/dryad.bvq83bk6f.
Article and author information
Author details
Funding
Wellcome Trust (WT 101885MA)
- Mohan K Balasubramanian
H2020 European Research Council (ERC-2014-ADG N{degree sign} 671083)
- Mohan K Balasubramanian
Wellcome Trust (ISSF-Warwick QBP RMRCB0058)
- Darius Vasco Köster
Department of Biotechnology, Ministry of Science and Technology, India (DBT-IISc partnership grant)
- Saravanan Palani
University of Warwick (Research development fund - RD19012)
- Scott Clarke
University of Warwick (International Chancellor's Fellowship)
- Sayantika Ghosh
University of Warwick (ARAP fellowship)
- Esther Ivorra-Molla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Palani 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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