한빛사논문
- 조회4,514
Abstract
Jihye Seonga, Arash Tajikb, Jie Sunc, Jun-Lin Guand, Martin J. Humphriese, Susan E. Craige, Asha Shekaranf, Andres J. Garciaf, Shaoying Luc, Michael Z. Ling, Ning Wangb,h,1, and Yingxiao Wanga,c,i,1
aNeuroscience Program,
bDepartment of Mechanical Science and Engineering, and
cDepartment of Bioengineering and Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL 61801;
dDivision of Molecular Medicine and Genetics and Department of Internal Medicine and Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109;
eWellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK;
fWoodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 48109;
gDepartment of Pediatrics and Bioengineering, Stanford University, Palo Alto, CA 94305;
hDepartment of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; and
iDepartment of Bioengineering, University of California, San Diego, CA 92093
Abstract
Matrix mechanics controls cell fate by modulating the bonds between integrins and extracellular matrix (ECM) proteins. However, it remains unclear how fibronectin (FN), type 1 collagen, and their receptor integrin subtypes distinctly control force transmission to regulate focal adhesion kinase (FAK) activity, a crucial molecular signal governing cell adhesion/migration. Here we showed, using a genetically encoded FAK biosensor based on fluorescence resonance energy transfer, that FN-mediated FAK activation is dependent on the mechanical tension, which may expose its otherwise hidden FN synergy site to integrin α5. In sharp contrast, the ligation between the constitutively exposed binding motif of type 1 collagen and its receptor integrin α2 was surprisingly tension-independent to induce sufficient FAK activation. Although integrin α subunit determines mechanosensitivity, the ligation between α subunit and the ECM proteins converges at the integrin β1 activation to induce FAK activation. We further discovered that the interaction of the N-terminal protein 4.1/ezrin/redixin/moesin basic patch with phosphatidylinositol 4,5-biphosphate is crucial during cell adhesion to maintain the FAK activation from the inhibitory effect of nearby protein 4.1/ezrin/redixin/moesin acidic sites. Therefore, different ECM proteins either can transmit or can shield from mechanical forces to regulate cellular functions, with the accessibility of ECM binding motifs by their specific integrin α subunits determining the biophysical mechanisms of FAK activation during mechanotransduction.
FRET biosensor, intracellular tension, substrate rigidity
1To whom correspondence may be addressed.
논문정보
- Research article
- 2013년 11월 (BRIC 등록일 2014-01-08)
- 국외 연구진
- 생명과학 > 세포생물학
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