Yang, Ming, James, Andrew David, Suman, Rakesh et al. (4 more authors) (2019) Voltage-dependent activation of Rac1 by Nav1.5 channels promotes cell migration. Journal of cellular physiology. ISSN 0021-9541
Abstract
Ion channels can regulate the plasma membrane potential (Vm) and cell migration as a result of altered ion flux. However, the mechanism by which Vm regulates motility remains unclear. Here, we show that the Nav1.5 sodium channel carries persistent inward Na+ current which depolarizes the resting Vm at the timescale of minutes. This Nav1.5-dependent Vm depolarization increases Rac1 colocalization with phosphatidylserine, to which it is anchored at the leading edge of migrating cells, promoting Rac1 activation. A genetically-encoded FRET biosensor of Rac1 activation shows that depolarization-induced Rac1 activation results in acquisition of a motile phenotype. By identifying Nav1.5-mediated Vm depolarization as a regulator of Rac1 activation, we link ionic and electrical signaling at the plasma membrane to small GTPase-dependent cytoskeletal reorganization and cellular migration. We uncover a novel and unexpected mechanism for Rac1 activation, which fine tunes cell migration in response to ionic and/or electric field changes in the local microenvironment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL (MRC) G1000508 |
Depositing User: | Pure (York) |
Date Deposited: | 01 Oct 2019 10:40 |
Last Modified: | 04 Nov 2024 01:21 |
Published Version: | https://doi.org/10.1002/jcp.29290 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1002/jcp.29290 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151538 |
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