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.
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Conference Article|
November 21 2011
The LINC complex and human disease
Peter Meinke;
Peter Meinke
1Institute of Human Genetics, Fleischmannstrasse 42-44, D-17475 Greifswald, Germany
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Thuy Duong Nguyen;
Thuy Duong Nguyen
1
1Institute of Human Genetics, Fleischmannstrasse 42-44, D-17475 Greifswald, Germany
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Manfred S. Wehnert
Manfred S. Wehnert
2
1Institute of Human Genetics, Fleischmannstrasse 42-44, D-17475 Greifswald, Germany
2To whom correspondence should be addressed (email mwehnert@uni-greifswald.de).
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Publisher: Portland Press Ltd
Received:
July 29 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (6): 1693–1697.
Article history
Received:
July 29 2011
Citation
Peter Meinke, Thuy Duong Nguyen, Manfred S. Wehnert; The LINC complex and human disease. Biochem Soc Trans 1 December 2011; 39 (6): 1693–1697. doi: https://doi.org/10.1042/BST20110658
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