title: Nesprins in health and disease.
abstract: LINC (Linker of Nucleoskeleton and Cytoskeleton) complex is an evolutionary conserved structure that spans the entire nuclear envelope (NE), and integrates the nuclear interior with the cytoskeleton, in order to support a diverse array of fundamental biological processes. Key components of the LINC complex are the nesprins (Nuclear Envelope SPectrin Repeat proteINS) that were initially described as large integral NE proteins. However, nesprin genes are complex and generate many variants, which occupy various sub-cellular compartments suggesting additional functions. Hence, the potential involvement of nesprins in disease has expanded immensely on what we already know. That is, nesprins are implicated in diseases such as cancer, myopathies, arthrogryposis, neurological disorders and hearing loss. Here we review nesprins by providing an in depth account of their structure, molecular interactions and cellular functions with relevance to their potential roles in disease. Specifically, we speculate about possible pathomechanisms underlying nesprin-associated diseases.
authors.affiliation: School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cartwright
authors.affiliation: School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK. Electronic address: iakowos.karakesisoglou@durham.ac.uk.
authors.forename: Iakowos
authors.initials: I
authors.lastname: Karakesisoglou
mesh_terms: D019588:Aging, Premature / Q000235:genetics; D000818:Animals; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016547:Kinesins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009140:Musculoskeletal Diseases / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics; D009685:Nuclear Envelope / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C488101:KIF5B protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C506117:SUN1 protein, human; C413025:SUN2 protein, human; C415465:SYNE1 protein, human; C485904:SYNE2 protein, human; C529565:SYNE3 protein, human; C539339:nesprin 4 protein, mouse; D016547:Kinesins
keywords: Ageing; Cancer; Cerebellar ataxia; LINC complex; Nesprin; SUN-domain proteins