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

Frederic F. Depreux, Megan J. Puckelwartz, Aleksandra Augustynowicz, Don Wolfgeher, Christine M. Labno, Dynora Pierre-Louis, Danielle Cicka, Stephen J. Kron, James Holaska, Elizabeth M. McNally

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4284-4295
Number of pages12
JournalHuman molecular genetics
Issue number15
StatePublished - Aug 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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