title: Nuclear membrane diversity: underlying tissue-specific pathologies in disease?
abstract: Human 'laminopathy' diseases result from mutations in genes encoding nuclear lamins or nuclear envelope (NE) transmembrane proteins (NETs). These diseases present a seeming paradox: the mutated proteins are widely expressed yet pathology is limited to specific tissues. New findings suggest tissue-specific pathologies arise because these widely expressed proteins act in various complexes that include tissue-specific components. Diverse mechanisms to achieve NE tissue-specificity include tissue-specific regulation of the expression, mRNA splicing, signaling, NE-localization and interactions of potentially hundreds of tissue-specific NETs. New findings suggest these NETs underlie tissue-specific NE roles in cytoskeletal mechanics, cell-cycle regulation, signaling, gene expression and genome organization. This view of the NE as 'specialized' in each cell type is important to understand the tissue-specific pathology of NE-linked diseases.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK. Electronic address: e.schirmer@ed.ac.uk.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
mesh_terms: D001692:Biological Transport; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D015398:Signal Transduction / Q000235:genetics
chemical_list: D009687:Nuclear Proteins