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
246 최광욱 교수, 홍성태 박사 Nature Communications 논문 게재(2016.09) / Prof. Kwang-Wook Choi and Dr. Sung-Tae Hong published a paper in Nature Communications 생명과학과 2016.10.06 5954
245 전상용 교수, 2009~2014 기초학문 약학분야 9위 선정 생명과학과 2016.10.04 7697
244 김정회 교수, 한국생명공학연합회 초대 회장에 선출 / Professor Jung-Hoe Kim elected to the first president of Korea association of Bioenginiering file 생명과학과 2016.08.26 7780
» 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 6992
242 최길주 교수, 김정현 박사과정 학생 The Plant Cell 게재(2016.06) / Prof. Giltsu Choi and Junghyun Kim, a Ph.D. candidate published a paper in The Plant Cell (2016.06) 생명과학과 2016.07.05 6742
241 이주용 박사, 김세윤 교수, PNAS지에 논문 게재 / PhD Joo-Yong Lee and Prof, Seyun Kim published a paper in PNAS 생명과학과 2016.07.04 8521
240 전상용 교수, 몸 속 물질 이용한 염증 치료제 개발 / Prof. Sang-Yong Jon developed anti-inflammatory drug using biological materials 생명과학과 2016.06.15 7550
239 정유진 석사과정 학생, 조병관 교수 Nature Communications 논문 게재(2016.06) / Yujin Jeong, a Master's degree student and Prof. Byung-Kwan Cho published a paper in Nature Communications (2016.06) 생명과학과 2016.06.07 6482
238 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 5899
237 김재현 박사과정 학생, 이승희 교수 J.Neurosci. 게재 (2016.05) / Jae-Hyun Kim and Prof. Seung-Hee Lee published article at J. Neurosci. (2016.05) 생명과학과 2016.05.18 7438
236 Thao Phuong Le 박사과정 학생, 최광욱 교수 Nature Communications 게재(2016.05) / Thao Phuong Le, a Ph.D candidate and Prof. Kwang-Wook Choi published a paper in Nature Communications (2016.05) 생명과학과 2016.05.12 5624
235 고창민 박사과정 학생, 최광욱 교수 Oncogene 게재(2016.04) / Chang Min Ko, a Ph.D candidate and Prof. Kwang-Wook Choi published a paper in Oncogene (2016.04) 생명과학과 2016.04.15 5602
234 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 6291
233 최길주 교수, KAIST 지정 석좌교수 임명 / Prof. Giltsu Choi is appointed KAIST-chair professor. 생명과학과 2016.03.16 7428
232 오병하 교수, 제 9회 아산의학상 수상 file 생명과학과 2016.03.14 8777
231 정형록 박사과정 학생, 최광욱 교수 Development Cell 게재(2016.02) / Hyung-Lok Chung, a Ph.D candidate and Prof. Kwang-Wook Choi published a paper in Dev. Cell (2016.02) 생명과학과 2016.03.11 6125
230 2015년 KAIST 대표 R&D 연구성과 10선 선정 / Announcement of KAIST's Top 10 Research Accomplishments of 2015 생명과학과 2016.03.07 5514
229 개교 45주년 기념 우수교원 수상 / Announcement of the 2016 Faculty Award Winners in Commemoration of the 45th Anniversary of Founding 생명과학과 2016.03.07 4592
228 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 6032
227 박우용 박사과정 학생(김미영 교수 실험실) Cancer Research 게재(2016.01) / Woo-Yong Park, a Ph.D candidate in Prof. Mi-Young Kim’s lab published a paper in Cancer Research (2016. 1) file 생명과학과 2016.01.22 8243
Board Pagination Prev 1 2 3 4 5 6 7 8 9 10 ... 14 Next
/ 14