LiNC Complex and Human Genetic Muscular Disease

Manfred S Wehnert, Institute of Human Genetics, Fleischmannstrasse, Greifswald, Germany
Peter Meinke, Institute of Human Genetics, Fleischmannstrasse, Greifswald, Germany

Published online: December 2012

DOI: 10.1002/9780470015902.a0024451

The linker of nucleoskeleton and cytoskeleton (LiNC) complex is a proposed mechanical link tethering the nucleo- and cytoskeleton via the nuclear envelope (NE). 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, cell- or tissue-specific LiNC complexes are also involved in signalling pathways and gene regulation. Emerin was the first LiNC component associated with a human disease, namely Emery–Dreifuss muscular dystrophy (EDMD). Later on, other components of a hypothetically muscle-specific LiNC complex, such as lamins A/C and small muscle-specific 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 47% of the EDMD patients can be linked to genes of LiNC and non-LiNC components, probably interacting with muscle-specific LiNC(s) involved in the pathology of muscular disorders.

Key Concepts:

  • Linker of nucleoskeleton and cytoskeleton (LiNC) complexes are tethering the nucleo- and cytoskeleton via the nuclear envelope.
  • The inhibition of LiNC components results in changes of the biomechanical behaviour of contractile cells.
  • Mutations in genes encoding muscle-specific LiNC components lead to a variety of inherited human muscular disorders, in particular Emery–Dreifuss muscular dystrophy.
  • The wide phenotypic variability of LiNC-associated muscular diseases can be explained by digenic inheritance.
  • The association of LiNC and LiNC-related components with human disease helps to resolve genetic heterogeneity and clinical variability and provides tools to understand their functions within the cell as well.

Keywords: LiNC complex; Emery–Dreifuss muscular dystrophy; neuromuscular disorders; lamin A/C; emerin; nesprin 1; nesprin 2; SUN1; SUN2

Figure 1. A Linker of Nucleoskeleton and Cytoskeleton (LiNC) complex at the nuclear envelope.
Figure 2. Clinical picture of Emery–Dreifuss muscular dystrophy in a 22-year-old patient: (a) Mild wasting of the upper arm and the lower leg muscles, contracture of the elbow tendons, pacemaker (arrow). (b) Rigid spine, mild contractures of the Achilles tendons. © Manfred Wehnert.
Figure 3. Segregation of mutations LMNA p.M348I and STA p.0 in a Belgian family. (Empty symbols – healthy individuals; filled symbols – affected individuals; hatched symbol – mildly affected individuals.)
Figure 4. Outcome of routine mutational analysis in 195 EDMD patients.
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Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Cytoskeleton | Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease
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Article Title: LiNC Complex and Human Genetic Muscular Disease
 
How to Cite close
Wehnert, Manfred S, and Meinke, Peter(Dec 2012) LiNC Complex and Human Genetic Muscular Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024451]