title: The nuclear envelope, a key structure in cellular integrity and gene expression.
abstract: The envelope that encapsulates the cell nucleus has recently gained considerable interest, as several clinical syndromes are linked to mutations in its molecular components. Most disorders recognized so far are caused by defects in the nuclear lamins, building blocks of a filamentous network lining the nucleoplasmic side of the inner nuclear membrane. Nuclear lamins are the evolutionary precursors of cytoskeletal intermediate filaments and associate in a head-to-tail manner into a stable lamina at the nuclear periphery and into a more dispersed structure in the nucleoplasm. Lamins have a scaffolding function for several nuclear processes such as transcription, chromatin organization and DNA replication, and maintain nuclear and cellular integrity. Mutations in the LMNA gene, encoding A-type lamins, can cause cardiac and skeletal muscle disease, lipodystrophy and premature ageing phenotypes. Hence, the integrity of the nuclear envelope seems essential for longevity. Furthermore, the laminopathies provide evidence that metabolism and ageing are as tightly linked in humans as they are in model organisms such as C. elegans. In this review, we elaborate on the structure and functions of nuclear lamins, the spectrum of syndromes related to mutations in nuclear envelope components and pathogenic concepts unifying these disorders.
authors.affiliation: Department of Dermatology, University Hospital Maastricht, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, The Netherlands. vve@sder.azm.nl
authors.forename: V L R M
authors.initials: VL
authors.lastname: Verstraeten
authors.forename: J L V
authors.initials: JL
authors.lastname: Broers
authors.forename: F C S
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: M A M
authors.initials: MA
authors.lastname: van Steensel
mesh_terms: D019588:Aging, Premature / Q000235:genetics; D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D004260:DNA Repair / Q000502:physiology; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics; D006570:Heterochromatin / Q000502:physiology; D006801:Humans; D034882:Lamins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D008060:Lipodystrophy / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics; D009685:Nuclear Envelope / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D034881:Nuclear Lamina / Q000502:physiology
chemical_list: D006570:Heterochromatin; D034882:Lamins