Nesprin-1 and actin contribute to nuclear and cytoskeletal defects in lamin A/C-deficient cardiomyopathy

► Disorganisation of the nuclear envelope and nesprin-1 in Lmna−/− cardiomyocytes. ► Enhanced osmotic stress responses suggest altered nuclear-cytoskeletal connections. ► Loss of lamin A/C is associated with heterogeneous distribution of nuclear G-actin. ► Nesprin-1 interacts with various cytoskeletal actin isoforms. ► Lmna−/− cardiomyocytes show increased cytoskeletal a-smooth muscle actin.