By the same authors

From the same journal

Voltage-dependent activation of Rac1 by Nav1.5 channels promotes cell migration

Research output: Contribution to journalArticle

Full text download(s)

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalJournal of cellular physiology
DateAccepted/In press - 30 Sep 2019
DateE-pub ahead of print (current) - 15 Oct 2019
Number of pages23
Early online date15/10/19
Original languageEnglish

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.

Bibliographical note

© 2019 The Authors

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations