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1 Janelia Publications

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    04/19/22 | Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole-cell mechanics.
    Vahabikashi A, Sivagurunathan S, Nicdao FA, Han YL, Park CY, Kittisopikul M, Wong X, Tran JR, Gundersen GG, Reddy KL, Luxton GW, Guo M, Fredberg JJ, Zheng Y, Adam SA, Goldman RD
    Proceedings of the National Academy of Sciences of the U.S.A.. 2022 Apr 19;119(17):e2121816119. doi: 10.1073/pnas.2121816119

    SignificanceInteractions between the cell nucleus and cytoskeleton regulate cell mechanics and are facilitated by the interplay between the nuclear lamina and linker of nucleoskeleton and cytoskeleton (LINC) complexes. To date, the specific contribution of the four lamin isoforms to nucleocytoskeletal connectivity and whole-cell mechanics remains unknown. We discover that A- and B-type lamins distinctively interact with LINC complexes that bind F-actin and vimentin filaments to differentially modulate cortical stiffness, cytoplasmic stiffness, and contractility of mouse embryonic fibroblasts (MEFs). We propose and experimentally verify an integrated lamin-LINC complex-cytoskeleton model that explains cellular mechanical phenotypes in lamin-deficient MEFs. Our findings uncover potential mechanisms for cellular defects in human laminopathies and many cancers associated with mutations or modifications in lamin isoforms.

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