ABSTRACT
Lamins are nuclear intermediate filaments which form a network like structure underneath the nuclear membrane, the nuclear lamina, as well as complexes in the nuclear interior. Lamins associate with numerous proteins in the inner nuclear membrane, in cluding emerin, and lamina-associated polypeptides. Beyond their structural roles lamins likely serve essential functions in many nuclear activities, such as DNA replication and transcription. Mutations in A-type lamins and emerin have been linked to at least eight rare human diseases (laminopathies), affecting skeletal and cardiac muscle, as well as fat, bone and neuronal tissues, or causing premature ageing. There is no clear genotype-phenotype relation of mutations, and it is still unknown, how mutations in the ubiquitously expressed lamin A and emerin cause tissue-restricted phenotypes. Focusing on neuromuscular laminopathies, we discuss potential disease mechanisms, including defects in lamin structure and assembly, misregulation of gene expression, perturbation of cell cycle control during tissue regeneration, and deregulation of metabolic and signaling functions of the endoplasmic reticulum.
