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
182 마 원 박사과정생(김은준 교수 Lab), 제3회 바이오니아 차세대 연구자상 대상 수상 과사무실 2011.09.21 8626
181 생명과학과 신임교원 David Helfman 박사 부임 소개 (2009.8.1) 과사무실 2009.09.10 8632
180 최은비 박사과정 학생(김미영 교수 실험실) Oncogene 게재(2016.02) / Eun-Bee Choi, a Ph.D candidate in Prof. Mi-Young Kim’s lab published a paper in Oncogene (2016.02) 생명과학과 2016.03.07 8635
179 김학성 교수, Nat. Chem. Biol. 게재 (2013.3) 과사무실 2013.03.22 8680
178 박태관 교수, 2010년 '올해의 KAIST인 상' 수상! 과사무실 2010.12.28 8702
177 과사무실 김미희님 - 2007년도 4/4분기 "이 달의 직원상" 수상 과사무실 2007.11.16 8711
176 2005학년도 석림학술장학재단 장학생 - 이영석 박사과정 학생 선정 과사무실 2005.12.29 8713
175 송민섭 박사 Agarwal Award (2004) 수상 과사무실 2004.11.08 8720
174 [한국경제] 고규영 교수 유력 바이오논문 6편 최다 발표 과사무실 2005.09.02 8729
173 권석규 학생(김은준 교수 lab), 2009' 석림학술장학재단 장학생으로 선정! 과사무실 2009.12.22 8730
172 2단계 BK21 1차년도 연차평가결과 -생물분야 1위! 과사무실 2007.10.10 8731
171 김학성교수...독일화학誌에 발표 과사무실 2007.08.01 8742
170 서연수 교수, 2009년 연구윤리 확립 유공자 교육과학기술부 장관 표창 수상! 과사무실 2010.01.06 8756
169 고규영 교수 국가지정연구실사업 신규과제 선정 과사무실 2004.08.23 8757
168 생명과학과 고규영 교수... 분쉬의학상 수상 과사무실 2007.10.29 8767
167 도민재, 박재윤, 정현정 (박태관 교수 lab), 2010' 특허전략 유니버시아드 장려상 수상! 과사무실 2010.12.20 8769
166 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 8779
165 전상용 교수, ACS Nano 게재(2014.2) 과사무실 2014.03.12 8796
164 박태관 교수, 획기적인 핵산 유전자 치료제 전달시스템 개발 과사무실 2010.01.30 8806
163 김진우 교수, EMBO Journal 에 논문 게재 (2012.2.15) 과사무실 2012.02.16 8806
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 15 Next
/ 15