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

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Title
PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front
Author(s)
Trang Thi Thu Nguyen; Wei Sun Park; Byung Ouk Park; Cha Yeon Kim; Yohan Oh; Jin Man Kim; Hana Choi; Taeyoon Kyung; cheol-Hee Kim; Gabsang Lee; Klaus M. Hahn; Tobias Meyer; Won Do Heo
Publication Date
2016-09
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.113, no.36, pp.10091 - 10096
Publisher
NATL ACAD SCIENCES
Abstract
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 ⓒNguyen et al.
URI
https://pr.ibs.re.kr/handle/8788114/3572
ISSN
0027-8424
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
Files in This Item:
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