YAP regulates cell mechanics by controlling focal adhesion assembly

被引：437

作者：

Nardone, Giorgia ^{[1
]}

La Cruz, Jorge Oliver-De ^{[1
]}

Vrbsky, Jan ^{[1
]}

Martini, Cecilia ^{[1
]}

Pribyl, Jan ^{[2
]}

Skladal, Petr ^{[2
]}

Pesl, Martin ^{[1
,3
]}

Caluori, Guido ^{[1
]}

Pagliari, Stefania ^{[1
]}

Martino, Fabiana ^{[1
,3
]}

Maceckova, Zuzana ^{[4
]}

Hajduch, Marian ^{[4
]}

Sanz-Garcia, Andres ^{[5
,6
]}

Pugno, Nicola Maria ^{[7
,8
,9
]}

Stokin, Gorazd Bernard ^{[1
]}

Forte, Giancarlo ^{[1
,10
]}

机构：

[1] St Annes Univ Hosp, ICRC, CZ-65691 Brno, Czech Republic

[2] Masaryk Univ, CEITEC MU, CZ-65691 Brno, Czech Republic

[3] Masaryk Univ, Dept Biol, Fac Med, CZ-62500 Brno, Czech Republic

[4] Palacky Univ Olomouc, Inst Mol & Translat Med, Fac Med & Dent, Hnevotinska 1333-5, CZ-77515 Olomouc, Czech Republic

[5] Univ Helsinki, Div Pharmaceut Biosci, Fac Pharm, Viikinkaari 5 E, FI-00014 Helsinki, Finland

[6] Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Shinjuku Ku, 8-1 Kawada Cho, JP-1628666 Tokyo, Japan

[7] Univ Trento, Dept Civil Environm & Mech Engn, Lab Bioinspired & Graphene Nanomech, I-38123 Trento, Italy

[8] Italian Space Agcy, Ket Lab, Via Politecn Snc, I-00133 Rome, Italy

[9] Queen Mary Univ London, Sch Engn & Mat Sci, Mile End Rd, London E1 4NS, England

[10] Univ Turku, Inst Dent, Dept Biomat Sci, FI-20014 Turku, Finland

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

欧洲研究理事会;

关键词：

ACTIN-FILAMENTS; SELF-RENEWAL; HIPPO; MIGRATION; PATHWAY; RAC; TAZ; YAP/TAZ; BINDING; PROTEIN;

D O I：

10.1038/ncomms15321

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

引用

页数：13

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