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Intermediate filaments and the regulation of focal adhesion

Leube RE, Moch M, Windoffer R, 2015

Focal adhesions are localized actin filament-anchoring signalling centres at the cell-extracellular matrix interface. The currently emerging view is that they fulfil an all-embracing coordinating function for the entire cytoskeleton. This review highlights the tight relationship between focal adhesions and the intermediate filament cytoskeleton. We summarize the accumulating evidence for direct binding of intermediate filaments to focal adhesion components and their mutual cross-talk through signalling molecules. Examples are presented to emphasize the high degree of complexity of these interactions equipping cells with a precisely controlled machinery for context-dependent adjustment of their biomechanical properties.

Keratin network re-organization and FA dynamics during the initial phase of cell migration. The time-lapse fluorescence micrographs and corresponding phase contrast images were recorded at 30 s intervals in A431-derived cell clone AK13-Pax9 stably expressing keratin 13-EGFP and paxillin-dsRed2. Cells had been cultivated for 48 h without fetal calf serum on a laminin 332-rich matrix. Migration was induced by complete medium change and addition of 50 ng ml1 EGF at time point 15 minutes. In response, the cell polarized and started to migrate toward the upper right corner. The paxillin-dsRed2-labeled FAs are rapidly turned over and translocate in the direction of movement. The - keratin network concentrates in the trailing edge and extends at the leading edge by addition of assembling precursor particles that appear in close vicinity of newly-formed FAs. Note the prominent keratin cage around the translocating nucleus. Bleaching of the FA signal was compensated for by contrast enhancement and Gaussian filtering. Bar, 10 μm.


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EGF enhances the formation of KF precursors in close vicinity of FAs. Clone AK13-Pax9 was cultivated and treated with EGF as described for Video 1. Treatment with EGF induced increased lamellipodia formation. Note that after EGF treatment new keratin precursors are formed in lamellipodia immediately after establishment of new FAs. The overall rate of keratin precursor formation and nucleation is enhanced in response to EGF treatment in parallel to increased FA formation. The keratin precursors grow into short filaments that fuse with each other and integrate into the inward-moving keratin network. Fluorescence signals were enhanced by using the rolling ball algorithm. Bar, 10 μm.


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