title: The nuclear lamina in health and disease.
abstract: The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases.
authors.affiliation: a Andalusian Center for Developmental Biology (CABD) , CSIC/Junta de Andalucia/Universidad Pablo de Olavide , Seville , Spain.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dobrzynska
authors.affiliation: b Edward A. Doisy Department of Biochemistry and Molecular Biology , St Louis University School of Medicine , St. Louis , MO , USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalo
authors.affiliation: c BHF Center for Research Excellence , King's College London, Cardiovascular Division, James Black Center , London , UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shanahan
authors.affiliation: a Andalusian Center for Developmental Biology (CABD) , CSIC/Junta de Andalucia/Universidad Pablo de Olavide , Seville , Spain.
authors.forename: Peter
authors.initials: P
authors.lastname: Askjaer
mesh_terms: D000818:Animals; D002465:Cell Movement; D002843:Chromatin / Q000378:metabolism; D004194:Disease; D006262:Health; D006801:Humans; D034881:Nuclear Lamina / Q000378:metabolism*
chemical_list: D002843:Chromatin
keywords: Hutchinson-Gilford progeria syndrome; LAP2; LBR; chromatin; emerin; farnesylation; laminopathies; mechanotransduction; metabolism; muscles; nuclear envelope; nuclear lamina