title: Nuclear lamina remodelling and its implications for human disease.
abstract: The intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies. These include cardiomyopathies, muscular dystrophies, lipodystrophies and progeroid syndromes. In addition, elevated levels of lamin B1, attributable to genomic duplications of the LMNB1 locus, cause adult-onset autosomal dominant leukodystrophy. The molecular mechanism(s) enabling the mutations and perturbations of the nuclear lamina to give rise to such a wide variety of diseases that affect various tissues remains unclear. The composition of the nuclear lamina changes dynamically during development, between cell types and even within the same cell during differentiation and ageing. Here, we discuss the functional and cellular aspects of lamina remodelling and their implications for the tissue-specific nature of laminopathies.
authors.affiliation: Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, Singapore, 138648, Republic of Singapore.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chojnowski
authors.forename: Peh Fern
authors.initials: PF
authors.lastname: Ong
authors.forename: Oliver
authors.initials: O
authors.lastname: Dreesen
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D004194:Disease / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D034882:Lamins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D034881:Nuclear Lamina / Q000473:pathology*
chemical_list: D034882:Lamins