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Voltage-dependent activation of Rac1 by Nav 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 Nav 1.5 sodium channel carries persistent inward Na+ current which depolarizes the resting Vm at the timescale of minutes. This Nav 1.5-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 Nav 1.5-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.

SUBMITTER: Yang M 

PROVIDER: S-EPMC6973152 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Voltage-dependent activation of Rac1 by Na<sub>v</sub> 1.5 channels promotes cell migration.

Yang Ming M   James Andrew D AD   Suman Rakesh R   Kasprowicz Richard R   Nelson Michaela M   O'Toole Peter J PJ   Brackenbury William J WJ  

Journal of cellular physiology 20191015 4


Ion channels can regulate the plasma membrane potential (V<sub>m</sub> ) and cell migration as a result of altered ion flux. However, the mechanism by which V<sub>m</sub> regulates motility remains unclear. Here, we show that the Na<sub>v</sub> 1.5 sodium channel carries persistent inward Na<sup>+</sup> current which depolarizes the resting V<sub>m</sub> at the timescale of minutes. This Na<sub>v</sub> 1.5-dependent V<sub>m</sub> depolarization increases Rac1 colocalization with phosphatidylseri  ...[more]

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