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
120 이주용 박사, 김세윤 교수, PNAS지에 논문 게재 / PhD Joo-Yong Lee and Prof, Seyun Kim published a paper in PNAS 생명과학과 2016.07.04 16038
119 이준식 교수 IAFOST Fellow 선출 과사무실 2003.09.08 13145
118 이중재 박사와 김학성 교수 연구팀, Theranostics에 표지 논문 발표 file 생명과학과 2017.08.18 12381
117 인선아 박사과정 학생. 제 18차 KHUPO 프로테오믹스 국제학술대회 수상 file 생명과학과 2018.04.13 12494
116 임대식 교수 국가지정연구실사업 신규과제 선정 과사무실 2005.03.30 11218
115 임대식 교수 논문 Nature Cell Biology 게재 1 과사무실 2004.01.26 13424
114 임대식 교수 외 3명 개교 34주년 기념 우수교원 포상 과사무실 2005.02.15 10671
113 임대식 교수, 2016년도 한국분자세포생물학회 정기학술대회 학술상 생명과학상 소개 강연 생명과학과 2016.10.10 13009
112 임대식 교수, EMBO Journal 에 논문 게재 (2012.3.7) 과사무실 2012.04.17 12388
111 임대식 교수, KAIST 지정 석좌교수 임용 과사무실 2014.02.25 11117
110 임대식 교수, PNAS 게재 (2013.4) 과사무실 2013.05.02 12311
109 임대식 교수, PNAS에 논문 게재! 과사무실 2010.04.21 11433
108 임대식 교수, 과학기술혁신본부장에 임명 file 생명과학과 2017.09.01 14867
107 임대식 교수, 교과부 ' 창의적연구진흥사업'의 신규 지원과제에 선정! 과사무실 2010.04.21 12121
106 임대식 교수, 김민철 박사 Cell Reports 에 논문 게재(2015.03) / Professor Dae-Sik Lim and Min Cheol Kim, Ph.D Publish in Cell Reports (2015.03) 과사무실 2015.04.06 13766
105 임대식 교수, 세포분열시 MST1 kinase의 새로운 암 억제 기능 발견 (2010. 3) 과사무실 2010.07.09 11328
104 임대식 교수, 천주교 서울대교구 생명위원회 제 14회 '생명의 신비상' 수상 file 생명과학과 2019.12.26 4274
103 임대식 교수, 한국과학상 대통령상 수상(2016. 12. 27) file 생명과학과 2016.12.28 12959
102 임대식 교수님 실험실 (김민철 박사과정) The Embo Journal 게재(2013.5) 과사무실 2013.07.05 14578
101 임대식 최길주 교수 승진 인사발령 과사무실 2004.09.01 13493
Board Pagination Prev 1 ... 9 10 11 12 13 14 15 16 17 18 19 Next
/ 19