Microtubule forces drive nuclear damage in LMNA cardiomyopathy.

ABSTRACT: Nuclear homeostasis requires balanced forces between the cytoskeleton and the nucleus. Mutations in LMNA, which encodes lamin A/C, weaken the nuclear lamina, leading to nuclear damage and muscle disease. Disrupting the linker of nucleoskeleton and cytoskeleton (LINC) complex, which connects the cytoskeleton to the nucleus, may ameliorate LMNA-associated cardiomyopathy, yet the cardioprotective mechanism remains unclear. Here we developed an assay to quantify the coupling between cardiomyocyte contraction and nuclear deformation and interrogate its dependence on the nuclear lamina and LINC complex. The LINC complex was mostly dispensable for transferring contractile strain to the nucleus, and its disruption did not rescue elevated nuclear strain in lamin A/C-deficient cardiomyocytes. Instea

SUBMITTER: Amiad Pavlov D 

PROVIDER: S-EPMC12611788 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature