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The LINC complex and human disease

The LINC complex and human disease The LINC (linker of nucleoskeleton and cytoskeleton) complex is a proposed mechanical link tethering the nucleo- and cyto-skeleton via the NE (nuclear envelope). The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins. Besides the mechanostructural functions, the LINC complex is also involved in signalling pathways and gene regulation. Emerin was the first LINC component associated with a human disease, namely EDMD (Emery–Dreifuss muscular dystrophy). Later on, other components of the LINC complex, such as lamins A/C and small isoforms of nesprin-1 and nesprin-2, were found to be associated with EDMD, reflecting a genetic heterogeneity that has not been resolved so far. Only approximately 46% of the EDMD patients can be linked to genes of LINC and non-LINC components, pointing to further genes involved in the pathology of EDMD. Obvious candidates are the LINC proteins SUN1 and SUN2. Recently, screening of binding partners of LINC components as candidates identified LUMA ( TMEM43 ), encoding a binding partner of emerin and lamins, as a gene involved in atypical EDMD. Nevertheless, such mutations contribute only to a very small fraction of EDMD patients. EDMD-causing mutations in STA / EMD (encoding emerin) that disrupt emerin binding to Btf (Bcl-2-associated transcription factor), GCL (germ cell-less) and BAF (barrier to autointegration factor) provide the first glimpses into LINC being involved in gene regulation and thus opening new avenues for functional studies. Thus the association of LINC with human disease provides tools for understanding its functions within the cell. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochemical Society Transactions Portland Press

The LINC complex and human disease

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Publisher
Portland Press
Copyright
Copyright by Portland Press
ISSN
0300-5127
DOI
10.1042/BST20110658
pmid
22103509
Publisher site
See Article on Publisher Site

Abstract

The LINC (linker of nucleoskeleton and cytoskeleton) complex is a proposed mechanical link tethering the nucleo- and cyto-skeleton via the NE (nuclear envelope). The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins. Besides the mechanostructural functions, the LINC complex is also involved in signalling pathways and gene regulation. Emerin was the first LINC component associated with a human disease, namely EDMD (Emery–Dreifuss muscular dystrophy). Later on, other components of the LINC complex, such as lamins A/C and small isoforms of nesprin-1 and nesprin-2, were found to be associated with EDMD, reflecting a genetic heterogeneity that has not been resolved so far. Only approximately 46% of the EDMD patients can be linked to genes of LINC and non-LINC components, pointing to further genes involved in the pathology of EDMD. Obvious candidates are the LINC proteins SUN1 and SUN2. Recently, screening of binding partners of LINC components as candidates identified LUMA ( TMEM43 ), encoding a binding partner of emerin and lamins, as a gene involved in atypical EDMD. Nevertheless, such mutations contribute only to a very small fraction of EDMD patients. EDMD-causing mutations in STA / EMD (encoding emerin) that disrupt emerin binding to Btf (Bcl-2-associated transcription factor), GCL (germ cell-less) and BAF (barrier to autointegration factor) provide the first glimpses into LINC being involved in gene regulation and thus opening new avenues for functional studies. Thus the association of LINC with human disease provides tools for understanding its functions within the cell.

Journal

Biochemical Society Transactions – Portland Press

Published: Dec 1, 2011

Keywords: Emery-Dreifuss muscular dystrophy (EDMD), linker of nucleoskeleton and cytoskeleton complex (LINC complex), neuromuscular disorder

References

  • Coupling of the nucleus and cytoplasm: role of the LINC complex
    Crisp
  • Dynamics and molecular interactions of linker of nucleoskeleton and cytoskeleton (LINC) complex proteins
    Östlund
  • Linear arrays of nuclear envelope proteins harness retrograde actin flow for nuclear movement
    Luxton
  • Altered mechanical properties of the nucleus in disease
    Lombardi
  • Molecular genetics of Emery–Dreifuss muscular dystrophy
    Morris
  • Emery–Dreifuss syndrome
    Emery
  • Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation
    Knoblauch
  • Severe clinical expression in X-linked Emery–Dreifuss muscular dystrophy
    Hoeltzenbein
  • Clinical and molecular genetic spectrum of autosomal dominant Emery–Dreifuss muscular dystrophy due to mutations of the lamin A/C gene
    Bonne
  • X-linked Emery–Dreifuss muscular dystrophy with lamin A deficiency and IBM inclusions
    Fidzianska
  • Myofiber degeneration in autosomal-dominant Emery–Dreifuss muscular dystrophy (AD-EDMD) (LGMD1B)
    Mittelbronn
  • Expression of lamin A mutated in the carboxyl-terminal domain generates a cell type sensitive aberrant nuclear phenotype similar to that observed in cells from patients with naturally occurring lamin A/C mutations
    Favreau
  • Nuclear envelope alterations and distinct localisation of nuclear proteins in a patient with a p. S143F mutation in the LMNA gene
    Kandert
  • Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy and partial lipodystrophy carrying lamin A/C gene mutations
    Muchir