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Cell-matrix adhesions are specialized protein complexes that anchor cells to the extracellular matrix. Besides being important for the integrity of tissues, they also function as relay stations that transmit signals from the outside to the inside of the cell and vice versa. Microtubules, which are part of the cytoskeleton, play an important role in the regulation of these adhesions. Microtubules are stabilized and anchored at the cell membrane close to cell-matrix adhesions by another protein complex, the cortical microtubule stabilizing complex (CMSC). KANK proteins play a central role in CMSCs.

In this thesis, we analyzed the role of KANK proteins in the interaction between cell-matrix adhesions and microtubules. We could show that KANK1 can directly bind to the cell-matrix adhesion protein talin. Thereby, KANK1 links cell-matrix adhesion complexes and the CMSC with each other. The talin-KANK1 interaction is necessary for the correct formation of the CMSC. The loss of KANK proteins leads to perturbed MT organization at the cell periphery.Besides, we discovered that the talin-KANK1 interaction is regulated by mechanical forces. Interestingly, the interaction gets first stronger when mechanical forces are pulling on the talin-KANK1 complex. In cells, this force regulation seems to affect the localization of KANK proteins.

Other aspects we studied were KANK proteins in cell migration and which other factors might contribute to the localization of KANK proteins in cells. Thereby, it seems that the KANK1 linker region L2 plays an important role in the localization, probably through a kind of self-association mechanism of KANK1.