FIGURE 1.

Overview on Lamin A/C proteins localization and on major mechanistic hypotheses underlying cardiac phenotypes. (A) Graphic representation of Lamin A/C proteins localization within the cell: Lamin A/C can be found both, at the periphery and in the nuclear interior. In the nucleus, Lamin A/C have a key structural function and are also involved in chromatin organization and regulation of genes transcription. This latter function can be mediated by both peripheral and nucleoplasmic Lamin A/C forms. Besides their role inside the nucleus, Lamin A/C also impact on cellular processes taking place at the outer part of the nuclear envelope: Lamin A/C indeed interact with the nucleo-cytoskeletal proteins, here indicated as LINC complex (i.e., SUN1, NESPRIN, intermediate filaments). The LINC proteins, in turn, interact with other cytoskeletal proteins (i.e., alpha-actinin), contributing to the maintenance of nuclear and cytoskeletal structure and effectors of specific signaling pathways. (B) The diagram shows the main mechanistic hypotheses underlying clinical manifestations of cardiolaminopathies. The arrows connecting the blue boxes indicate that these hypotheses are not mutually exclusive, but, instead, are potentially interconnected and all contribute to the final phenotype. (C) Clinical manifestations typically associated to LMNA-CMP.