Nuclear talin-1 provides a bridge between cell adhesion and gene expression
: Da Silva, Alejandro J.; Hästbacka, Hendrik S. E.; Puustinen, Mikael C.; Pessa, Jenny C.; Luoto, Jens C.; Sundström, Erika; Goult, Benjamin T.; Jacquemet, Guillaume; Henriksson, Eva; Sistonen, Lea
Publisher: Cell Press
: CAMBRIDGE
: 2025
: iScience
: iScience
: ISCIENCE
: 111745
: 28
: 2
: 111745
: 18
: 2589-0042
: 2589-0042
DOI: https://doi.org/10.1016/j.isci.2025.111745
: https://doi.org/10.1016/j.isci.2025.111745
: https://research.utu.fi/converis/portal/detail/Publication/485078218
Talin-1 (TLN1) is best known to activate integrin receptors and transmit mechanical stimuli to the actin cytoskeleton at focal adhesions. However, the localization of TLN1 is not restricted to focal adhesions. By utilizing both subcellular fractionations and confocal microscopy analyses, we show that TLN1 localizes to the nucleus in several human cell lines, where it is tightly associated with the chromatin. Importantly, small interfering RNA (siRNA)-mediated depletion of endogenous TLN1 triggers extensive changes in the gene expression profile of human breast epithelial cells. To determine the functional impact of nuclear TLN1, we expressed a TLN1 fusion protein containing a nuclear localization signal. Our findings revealed that the accumulation of nuclear TLN1 alters the expression of a subset of genes and impairs the formation of cell-cell clusters. This study introduces an additional perspective on the canonical view of TLN1 subcellular localization and function.
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This work has been funded by the Research Council of Finland (338537 to G.J. and 355596 to L.S.), Sigrid Jusélius Foundation (G.J. and L.S.), Cancer Foundation Finland (G.J. and L.S.), Centre for International Mobility (A.J.D.S. and E.H.), Ella and Georg Ehrnrooth Foundation (A.J.D.S. and H.S.E.H.), Finnish Cultural Foundation (A.J.D.S.), K. Albin Johansson Foundation (A.J.D.S. and E.H.), InFLAMES Flagship Programme of the Research Council of Finland (decision numbers: 337530, 337531, 357910, and 357911 to G.J.), Magnus Ehrnrooth Foundation (A.J.D.S., J.C.L., and E.H.), Medicinska Understödsföreningen Liv och Hälsa r.f. (A.J.D.S., E.H., and L.S.), Otto A. Malm Foundation (A.J.D.S.), The Maud Kuistila Memorial Foundation (H.S.E.H.), Solutions for Health strategic funding to Åbo Akademi University (G.J.), and Åbo Akademi University (A.J.D.S., J.C.P., and L.S.).