A subpopulation of Talin 1 resides in the nucleus and regulates gene expression

Abstract

Talin 1 (TLN1) is best known for its role at focal adhesions, where it activates β-integrin receptors and transmits mechanical stimuli to the actin cytoskeleton. Interestingly, the localization of TLN1 is not restricted to the focal adhesions, but its function in other cellular compartments remains poorly understood. By utilizing both biochemical and confocal microscopy analyses, we show that TLN1 localizes to the nucleus and that it strongly interacts with the chromatin. Importantly, depletion of endogenous TLN1 results in extensive changes in the gene expression profile of human breast epithelial cells. To determine the impact of nuclear TLN1 on gene regulation, we expressed a TLN1 fusion protein containing a nuclear localization signal. Our results revealed that nuclear TLN1 regulates a specific subset of the TLN1-dependent genes. Taken together, we show that apart from localizing at the plasma membrane and cytoplasm, TLN1 also resides in the nucleus where it functions in the regulation of gene expression.

pH-Selective Reactions to Selectively Reduce Cancer Cell Proliferation: Effect of CaS Nanostructures in Human Skin Melanoma and Benign Fibroblasts

“…In cancer cells, on the other hand, the mechanism is not properly regulated and FAK is overexpressed [ 39 – 41 ]. Control melanoma cells have significant focal points and vinculin around the nucleus, the latter likely resulting from interactions with talin localized in the cell nucleus [ 42 , 43 ]. In treated melanoma cells, we found vinculin to be delocalized over the entire cytoplasmic fluid, consistent with an increase in its inactive form, which is consistent with the activation of FAK regulation mechanisms [ 44 ].…”

FERM domain–containing proteins are active components of the cell nucleus

“…Talin contains an N-terminal FERM domain that binds and regulates the conformation of the integrin receptor and induces intracellular force sensing, and a C-terminal F-actin–binding domain ( Fig 2 ). In human epithelial cells, talin-1 was found recently in the nucleus, where it interacts with the chromatin and localizes primarily to the nucleolus ( Da Silva et al, 2022 Preprint ). In Drosophila , the talin homologue (rhea) regulates DE-cadherin at the transcriptional level; however, at present, it seems more likely that talin acts in the cytoplasm to control the activity of a transcriptional factor rather than being directly involved in gene expression in the nucleus ( Bécam et al, 2005 ).…”

Working a second job: Cell adhesion proteins that moonlight in the nucleus

“…Talin-1 is another important adaptor protein, mediating both mechanical dependent signaling and binding to the Actin cytoskeleton. Recently, Talin - 1 was shown to localize to the nucleus, bind chromatin, and when nuclear localization was enhanced with addition of a genetic nuclear localization signal, gene expression changes were observed ( Da Silva et al, 2022 ).…”

“…The nuclear function of three of the focal adhesion proteins, Talin-1, FAK, and Zyxin have been explored to some detail. For instance, a recent paper demonstrated that Talin-1 depletion altered gene expression and was copurified with the chromatin fraction of cells ( Da Silva et al, 2022 ), but the direct result of this interaction is yet forthcoming. Importantly, the relevance of this nuclear localization of Talin-1 in both development and disease remains a key question.…”