Nudel and FAK as Antagonizing Strength Modulators of Nascent Adhesions through Paxillin

Competition for binding to the cellular protein paxillin by the proteins Nudel and focal adhesion kinase is important for the proper regulation of cell adhesion and migration

Synopsis and meta-analysis of genetic association studies in osteoporosis for the focal adhesion family genes: the CUMAGAS-OSTEOporosis information system

<p>Abstract</p> <p>Background</p> <p>Focal adhesion (FA) family genes have been studied as candidate genes for osteoporosis, but the results of genetic association studies (GASs) are controversial. To clarify these data, a systematic assessment of GASs for FA genes in osteoporosis was conducted.</p> <p>Methods</p> <p>We developed Cumulative Meta-Analysis of GAS-OSTEOporosis (CUMAGAS-OSTEOporosis), a web-based information system that allows the retrieval, analysis and meta-analysis (for allele contrast, recessive, dominant, additive and codominant models) of data from GASs on osteoporosis with the capability of update. GASs were identified by searching the PubMed and HuGE PubLit databases.</p> <p>Results</p> <p>Data from 72 studies involving 13 variants of 6 genes were analyzed and catalogued in CUMAGAS-OSTEOporosis. Twenty-two studies produced significant associations with osteoporosis risk under any genetic model. All studies were underpowered (<50%). In four studies, the controls deviated from the Hardy-Weinberg equilibrium. Eight variants were chosen for meta-analysis, and significance was shown for the variants collagen, type I, α₁(<it>COL1A1</it>) G2046T (all genetic models), <it>COL1A1 </it>G-1997T (allele contrast and dominant model) and integrin β-chain β₃(<it>ITGB3</it>) T176C (recessive and additive models). In <it>COL1A1 </it>G2046T, subgroup analysis has shown significant associations for Caucasians, adults, females, males and postmenopausal women. A differential magnitude of effect in large versus small studies (that is, indication of publication bias) was detected for the variant <it>COL1A1 </it>G2046T.</p> <p>Conclusion</p> <p>There is evidence of an implication of FA family genes in osteoporosis. CUMAGAS-OSTEOporosis could be a useful tool for current genomic epidemiology research in the field of osteoporosis.</p

Differential effect of actomyosin relaxation on the dynamic properties of focal adhesion proteins

Treatment of cultured cells with inhibitors of actomyosin contractility induces rapid deterioration of stress fibers, and disassembly of the associated focal adhesions (FAs). In this study, we show that treatment with the Rho kinase inhibitor Y-27632, which blocks actomyosin contractility, induces disarray in the FA-associated actin bundles, followed by the differential dissociation of eight FA components from the adhesion sites. Live-cell microscopy indicated that the drug triggers rapid dissociation of VASP and zyxin from FAs (τ values of 7-8 min), followed by talin, paxillin and ILK (τ ~16 min), and then by FAK, vinculin and kindlin-2 (τ = 25-28 min). Examination of the molecular kinetics of the various FA constituents, using Fluorescence Recovery After Photobleaching (FRAP), in the absence of or following short-term treatment with the drug, revealed major changes in the kon and koff values of the different proteins tested, which are in close agreement with their differential dissociation rates from the adhesion sites. These findings indicate that mechanical, actomyosin-generated forces differentially regulate the molecular kinetics of individual FA-associated molecules, and thereby modulate FA composition and stability