KAIST 생명과학과동창회
  • News & Events
  • News

News

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

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, and Won Do Heo#

 

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.

 

Significance

Polarized cell migration plays a pivotal role in the development and repair of tissues. PI3K, RhoGTPases, and actin filaments are known to be involved in a positive feedback loop that induces and maintains cell polarity. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) selectively binds to newly polymerized actin and that this interaction exerts a positive regulatory effect on PLEKHG3 activity that enhances and sustains the cell front. A lack of PLEKHG3 ablates cell polarity, resulting in a decrease in cell migration. These findings provide the missing link that explains how Ras-related C3 botulinum toxin substrate 1 (Rac1) and actin polymerization are coupled by a positive feedback loop to ensure the stability of cell polarity.


List of Articles
번호 제목 글쓴이 날짜 조회 수
284 홍철암 박사과정(김학성 교수 Lab), ICMAT 2011에서 The Best Poster Award 수상! 과사무실 2011.07.06 10452
283 홍성태 박사, 하국선 박사, 2011년도 이공분야 "학문후속양성사업" 선정! 과사무실 2011.09.16 10916
282 허원도,김대수,한용만 교수 공동연구팀,Nature Biotechnology지에 표지논문 게재 file 생명과학과 2015.10.12 33535
281 허원도 교수와 양희원, 최하나 학생 Freshman Design Course에서 최우수상 수상! 과사무실 2009.09.07 10269
280 허원도 교수, 심장질환 원인신호 전달 메커니즘 규명 과사무실 2010.12.20 10784
279 허원도 교수, 빛만 비춰도 유전자 발현 조절하는 효소 개발 file 생명과학과 2019.01.21 1462
278 허원도 교수, 변화무쌍 스위치 단백질 관찰하는 바이오센서 개발 file 생명과학과 2019.01.16 2337
277 허원도 교수, 박혜림 박사, 김나연 박사과정 학생 Nature Communications지 논문 게재(2017.06) file 생명과학과 2017.06.26 10592
276 허원도 교수, 김진만 박사, 이민지 박사과정 학생 PNAS지에 논문 게재(2016.05) / Prof. Won-Do Heo, PhD. Jin-Man Kim and Min-Ji lee publish an article in PNAS (2016.05) 생명과학과 2016.05.18 8223
» 허원도 교수, Trang T. T. Nguyen박사 PNAS지에 논문 게재(2016.08) / Prof. Won Do Heo, PhD. Trang T. T. Nguyen publish an article in PNAS (2016.08) 생명과학과 2016.08.25 9594
274 허원도 교수, Nature Methods 게재 (2014. 5) 과사무실 2014.05.08 15299
273 허원도 교수, Nature Communications지 논문 게재 (2014. 6) 과사무실 2014.06.05 9749
272 허원도 교수, Nature Communications 게재(2013.2) 과사무실 2013.02.22 10854
271 허원도 교수, Mol Cell 과 JMCB 에 논문 게재! 과사무실 2012.06.11 11219
270 허원도 교수, Mai Khanh Nguyen 박사과정 학생 Nature Chemical Biology 논문 게재(2016.04) / Prof. Won Do Heo and Mai Khanh Nguyen Ph.D. published a paper in a Nature Chemical Biology(2016.04) 생명과학과 2016.04.12 8890
269 허원도 교수, ECLIPSE 기술 개발 PNAS지 게재 과사무실 2010.02.10 9261
268 허원도 교수, Chemistry & Biology지 표지논문 게재 과사무실 2014.07.22 10713
267 허원도 교수, 2017년도 4월 「이달의 과학기술인상」 으로 선정 생명과학과 2017.02.07 12107
266 한진희 교수님 실험실 (김지은 Post-doc, 권정태 박사과정) Nature Neuroscience 개제 과사무실 2014.01.21 11733
265 한진희 교수, 원혜정 학생(김은준 교수 Lab) 2009' 청암 과학펠로 선정! 과사무실 2009.11.27 10527
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 15 Next
/ 15