Voltage-dependent activation of Rac1 by Na v 1.5 channels promotes cell migration
Voltage-dependent activation of Rac1 by Na v 1.5 channels promotes cell migration
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.
Yang Ming、Kasprowicz Richard、Nelson Michaela、James Andrew D.、Suman Rakesh、O?ˉToole Peter J.、Brackenbury William J.
Department of Biology, University of YorkPhase Focus Ltd, Electric Works, Sheffield Digital CampusDepartment of Biology, University of York||York Biomedical Research Institute, University of York, HeslingtonDepartment of Biology, University of York||York Biomedical Research Institute, University of York, HeslingtonPhase Focus Ltd, Electric Works, Sheffield Digital CampusBioscience Technology Facility, Department of Biology, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of York, Heslington
基础医学生物科学理论、生物科学方法生理学
Breast cancermembrane potentialmigrationNav1.5Rac1
Yang Ming,Kasprowicz Richard,Nelson Michaela,James Andrew D.,Suman Rakesh,O?ˉToole Peter J.,Brackenbury William J..Voltage-dependent activation of Rac1 by Na v 1.5 channels promotes cell migration[EB/OL].(2025-03-28)[2025-08-07].https://www.biorxiv.org/content/10.1101/597088.点此复制
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