Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins

• Published in: EMBO reports Vol. 12; no. 3; pp. 259 - 266
• Main Authors: Schiller, Herbert B, Friedel, Caroline C, Boulegue, Cyril, Fässler, Reinhard
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2011; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Adhesion; Animals; Cell Adhesion; Cell adhesion & migration; Cells, Cultured; Cellular biology; EMBO05; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; focal adhesion; Focal Adhesions - genetics; Focal Adhesions - metabolism; Heterocyclic Compounds, 4 or More Rings - pharmacology; integrin adhesome; Integrins - metabolism; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - metabolism; LIM domain; Mass Spectrometry; Mice; Myosin Type II - antagonists & inhibitors; Myosin Type II - metabolism; myosin-II; Proteins; Proteomics; quantitative proteomics; Scientific Report; Scientific Reports; Signal Transduction; Zinc Fingers; focal adhesion; LIM domain; quantitative proteomics; integrin adhesome; myosin‐II
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2011.5

A characteristic of integrins is their ability to transfer chemical and mechanical signals across the plasma membrane. Force generated by myosin II makes cells able to sense substrate stiffness and induce maturation of nascent adhesions into focal adhesions. In this paper, we present a comprehensive proteomic analysis of nascent and mature adhesions. The purification of integrin adhesion complexes combined with quantitative mass spectrometry enabled the identification and quantification of known and new adhesion‐associated proteins. Furthermore, blocking adhesion maturation with the myosin II inhibitor blebbistatin markedly impaired the recruitment of LIM domain proteins to integrin adhesion sites. This suggests a common recruitment mechanism for a whole class of adhesion‐associated proteins, involving myosin II and the zinc‐finger‐type LIM domain. Myosin II drives growth and maturation of integrin mediated cell‐ECM contacts. Quantitative proteomic analysis of the integrin‐associated sub‐proteome reveals a myosin‐II‐dependent protein‐recruitment mechanism involving the zinc‐finger type LIM domain.