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Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy.
J Cell Sci. 2001 Dec; 114(Pt 24):4435-45.JC

Abstract

Autosomal dominant Emery-Dreifuss muscular dystrophy is caused by mutations in the LMNA gene, which encodes lamin A and lamin C. Mutations in this gene also give rise to limb girdle muscular dystrophy type 1B, dilated cardiomyopathy with atrioventricular conduction defect and Dunnigan-type partial lipodystrophy. The properties of the mutant lamins that cause muscular dystrophy, lipodystrophy and dilated cardiomyopathy are not known. We transfected C2C12 myoblasts with cDNA encoding wild-type lamin A and 15 mutant forms found in patients affected by these diseases. Immunofluorescence microscopy showed that four mutants, N195K, E358K, M371K and R386K, could have a dramatically aberrant localization, with decreased nuclear rim staining and formation of intranuclear foci. The distributions of endogenous lamin A/C, lamin B1 and lamin B2 were also altered in cells expressing these four mutants and three of them caused a loss of emerin from the nuclear envelope. In the yeast two-hybrid assay, the 15 lamin A mutants studied interacted with themselves and with wild-type lamin A and lamin B1. Pulse-chase experiments showed no decrease in the stability of several representative lamin A mutants compared with wild-type. These results indicate that some lamin A mutants causing disease can be aberrantly localized, partially disrupt the endogenous lamina and alter emerin localization, whereas others localize normally in transfected cells.

Authors+Show Affiliations

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11792809

Citation

Ostlund, C, et al. "Properties of Lamin a Mutants Found in Emery-Dreifuss Muscular Dystrophy, Cardiomyopathy and Dunnigan-type Partial Lipodystrophy." Journal of Cell Science, vol. 114, no. Pt 24, 2001, pp. 4435-45.
Ostlund C, Bonne G, Schwartz K, et al. Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. J Cell Sci. 2001;114(Pt 24):4435-45.
Ostlund, C., Bonne, G., Schwartz, K., & Worman, H. J. (2001). Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. Journal of Cell Science, 114(Pt 24), 4435-45.
Ostlund C, et al. Properties of Lamin a Mutants Found in Emery-Dreifuss Muscular Dystrophy, Cardiomyopathy and Dunnigan-type Partial Lipodystrophy. J Cell Sci. 2001;114(Pt 24):4435-45. PubMed PMID: 11792809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. AU - Ostlund,C, AU - Bonne,G, AU - Schwartz,K, AU - Worman,H J, PY - 2002/1/17/pubmed PY - 2002/3/22/medline PY - 2002/1/17/entrez SP - 4435 EP - 45 JF - Journal of cell science JO - J Cell Sci VL - 114 IS - Pt 24 N2 - Autosomal dominant Emery-Dreifuss muscular dystrophy is caused by mutations in the LMNA gene, which encodes lamin A and lamin C. Mutations in this gene also give rise to limb girdle muscular dystrophy type 1B, dilated cardiomyopathy with atrioventricular conduction defect and Dunnigan-type partial lipodystrophy. The properties of the mutant lamins that cause muscular dystrophy, lipodystrophy and dilated cardiomyopathy are not known. We transfected C2C12 myoblasts with cDNA encoding wild-type lamin A and 15 mutant forms found in patients affected by these diseases. Immunofluorescence microscopy showed that four mutants, N195K, E358K, M371K and R386K, could have a dramatically aberrant localization, with decreased nuclear rim staining and formation of intranuclear foci. The distributions of endogenous lamin A/C, lamin B1 and lamin B2 were also altered in cells expressing these four mutants and three of them caused a loss of emerin from the nuclear envelope. In the yeast two-hybrid assay, the 15 lamin A mutants studied interacted with themselves and with wild-type lamin A and lamin B1. Pulse-chase experiments showed no decrease in the stability of several representative lamin A mutants compared with wild-type. These results indicate that some lamin A mutants causing disease can be aberrantly localized, partially disrupt the endogenous lamina and alter emerin localization, whereas others localize normally in transfected cells. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/11792809/Properties_of_lamin_A_mutants_found_in_Emery_Dreifuss_muscular_dystrophy_cardiomyopathy_and_Dunnigan_type_partial_lipodystrophy_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11792809 DB - PRIME DP - Unbound Medicine ER -