Talin as a novel regulator of gene expression

Talin1 is a focal adhesion adaptor protein that has been described as a master regulator of integrin-mediated adhesion, linking cell-ECM receptors to the cell cytoskeleton. It was recently shown that a sub-population of TLN1 resides in the nucleus and regulates gene expression. We hypothesize that this provides a novel layer of regulation by TLN1 and an unexplored mechanism for TLN1 to contribute to cancer progression. We specifically aim to understand what influences Talin to translocate to the nucleus, and thus its ability to alter gene expression. This will be explored in two contexts. The first is to alter known Talin functions at FAs such as integrin activation, actin binding and autoinhibition. We predict that enhancing these functions may prevent TLN1 nuclear localization as it remains functionally bound at FAs. Changes in TLN1 localization patterns will be observed via immunofluorescence and then correlated to gene expression changes with RNA-seq. In the second context we will use Transforming Growth Factor-β as an external stimuli to drive epithelial to mesenchymal transition. We will observe Talin localization via quantitative immunofluorescence and correlate this to gene expression changes with RNA-seq. We hypothesize that this may increase Talin’s nuclear role.