Analysis of the myosinII-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation
By Jean-Cheng Kuo, Xuemei Han, Cheng-Te Hsiao, John R. Yates III, Clare M. Waterman. Nature Cell Biology, 2011
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Focal adhesions undergo myosin-II-mediated maturation wherein they grow and change composition to modulate integrin signalling for cell migration, growth and differentiation. To determine how focal adhesion composition is affected by myosin II activity, we performed proteomic analysis of isolated focal adhesions and compared protein abundance in focal adhesions from cells with and without myosin II inhibition. We identified 905 focal adhesion proteins, 459 of which changed in abundance with myosin II inhibition, defining the myosin-II-responsive focal adhesion proteome. The abundance of 73% of the proteins in the myosin-II-responsive focal adhesion proteome was enhanced by contractility, including proteins involved in Rho-mediated focal adhesion maturation and endocytosis- and calpain-dependent focal adhesion disassembly. During myosin II inhibition, 27% of proteins in the myosin-II-responsive focal adhesion proteome, including proteins involved in Rac-mediated lamellipodial protrusion, were enriched in focal adhesions, establishing that focal adhesion protein recruitment is also negatively regulated by contractility. We focused on the Rac guanine nucleotide exchange factor β-Pix, documenting its role in the negative regulation of focal adhesion maturation and the promotion of lamellipodial protrusion and focal adhesion turnover to drive cell migration.
Subfields: Cell Biology, Immunology and Allergy, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/30446f23ae4b48c0452f5e18ef54ba5335d88884
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Citations in the corpus
- Physics of adherent cells (2013, background): “The detailed molecular organization of focal adhesions is a very active area of research that is very challenging due to the large number (more than 150) of different components that are involved (Kuo et al., 2011; ZaidelBar et al., 2007).”
- Integrin-mediated mechanotransduction (2016, background): “Other system-level changes in the integrin adhesome have been observed during tension release and adhesion turnover, suggesting high plasticity and mechanosensitivity of the adhesome network (Kuo et al., 2011; Horton et al., 2015).”