PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front

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Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration
Publisher
NATL ACAD SCIENCES
Issue Date
2016-09
Language
English
Article Type
Article
Keywords

NUCLEOTIDE EXCHANGE FACTORS; BINDING PROTEIN; NEUTROPHIL CHEMOTAXIS; DISTINCT ROLES; RHO-GTPASES; PDZ-RHOGEF; CORONIN 1B; F-ACTIN; MOTILITY; FAMILY

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.113, no.36, pp.10091 - 10096

ISSN
0027-8424
DOI
10.1073/pnas.1604720113
URI
http://hdl.handle.net/10203/213498
Appears in Collection
BS-Journal Papers(저널논문)
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