Abstract
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.
| Original language | English |
|---|---|
| Article number | 111745 |
| Journal | iScience |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 21 Feb 2025 |
| MoE publication type | A1 Journal article-refereed |
Funding
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 ja Georg Ehrnrooth's 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’s 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.). We thank all the members of Sistonen laboratory for expert support during the preparation of the manuscript. The Cell Imaging and Cytometry Core facility (Turku Bioscience, University of Turku, Åbo Akademi University, and Biocenter Finland) and Turku Bioimaging are acknowledged for services, instrumentation, and expertise. We thank Markku Saari, Jouko Sandholm, and Christoffer Lagerholm from the Cell Imaging Core of Turku Bioscience Center for technical assistance and advice. We thank Joanna Pylvänäinen for her assistance with image analysis. Mass spectrometry analyses were performed at the Turku Proteomics Facility supported by Biocenter Finland. The Finnish Functional Genomics Center (Turku Bioscience, University of Turku, Åbo Akademi University and Biocenter Finland) is acknowledged for services, instrumentation, and expertise.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.).