期刊
JOURNAL OF CELL BIOLOGY
卷 205, 期 2, 页码 265-281出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201308136
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资金
- Nevus Outreach
- Swiss National Science foundation [31003A-130742]
- Swiss Foundation for Research on Myopothies
- Karlsruhe School of Optics and Photonics
- Academy of Finland
- Sigrid Juselius Foundation
- Competitive State Research Financing of Expert Responsibility Area of Tampere University Hospital
- Swiss National Science Foundation (SNF) [31003A_130742] Funding Source: Swiss National Science Foundation (SNF)
Integrin-dependent cell adhesion and spreading are critical for morphogenesis, tissue regeneration, and immune defense but also tumor growth. However, the mechanisms that induce integrin-mediated cell spreading and provide mechanosensing on different extracellular matrix conditions are not fully understood. By expressing beta 3-GFP-integrins with enhanced talin-binding affinity, we experimentally uncoupled integrin activation, clustering, and substrate binding from its function in cell spreading. Mutational analysis revealed Tyr747, located in the first cytoplasmic NPLY747 motif, to induce spreading and paxillin adapter recruitment to substrate- and talin-bound integrins. In addition, integrin-mediated spreading, but not focal adhesion localization, was affected by mutating adjacent sequence motifs known to be involved in kindlin binding. On soft, spreading-repellent fibronectin substrates, high-affinity talin-binding integrins formed adhesions, but normal spreading was only possible with integrins competent to recruit the signaling adapter protein paxillin. This proposes that integrin-dependent cell matrix adhesion and cell spreading are independently controlled, offering new therapeutic strategies to modify cell behavior in normal and pathological conditions.
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