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Hum Mol Genet. 2015 Aug 1;24(15):4284-95. doi: 10.1093/hmg/ddv160. Epub 2015 May 6.

Disruption of the lamin A and matrin-3 interaction by myopathic LMNA mutations.

Author information

1
Department of Medicine.
2
Department of Medicine, Center for Genetic Medicine, Northwestern University, Chicago, IL, 60611, USA.
3
Department of Molecular of Genetics and Cell Biology, Proteomics Core Facility.
4
Integrated Microscopy Facility, Office of Shared Research Facilities.
5
Department of Molecular of Genetics and Cell Biology.
6
Department of Medicine, Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA and Center for Genetic Medicine, Northwestern University, Chicago, IL, 60611, USA elizabeth.mcnally@northwestern.edu.

Abstract

The nuclear face of the nuclear membrane is enriched with the intermediate filament protein lamin A. Mutations in LMNA, the gene encoding lamin A, lead to a diverse set of inherited conditions including myopathies that affect both the heart and skeletal muscle. To gain insight about lamin A protein interactions, binding proteins associated with the tail of lamin A were characterized. Of 130 nuclear proteins found associated with the lamin A tail, 17 (13%) were previously described lamin A binding partners. One protein not previously linked to lamin A, matrin-3, was selected for further study, because like LMNA mutations, matrin-3 has also been implicated in inherited myopathy. Matrin-3 binds RNA and DNA and is a nucleoplasmic protein originally identified from the insoluble nuclear fraction, referred to as the nuclear matrix. Anti-matrin-3 antibodies were found to co-immunoprecipitate lamin A, and the lamin-A binding domain was mapped to the carboxy-terminal half of matrin-3. Three-dimensional mapping of the lamin A-matrin-3 interface showed that the LMNA truncating mutation Δ303, which lacks the matrin-3 binding domain, was associated with an increased distance between lamin A and matrin-3. LMNA mutant cells are known to have altered biophysical properties and the matrin-3-lamin A interface is positioned to contribute to these defects.

PMID:
25948554
PMCID:
PMC4492393
DOI:
10.1093/hmg/ddv160
[Indexed for MEDLINE]
Free PMC Article

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