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Increased solubility of lamins and redistribution of lamin C in X-linked Emery Dreifuss Muscular Dystrophy Fibroblasts

Markiewicz, E.; Venables, R.; Alvarez-Reyes, M.; Quinlan, R.; Dorobek, M.; Hausmanowa-Petrusewicz, I.; Hutchison, C.

Authors

E. Markiewicz

R. Venables

M. Alvarez-Reyes

R. Quinlan

M. Dorobek

I. Hausmanowa-Petrusewicz

C. Hutchison



Abstract

Emery–Dreifuss muscular dystrophy (EDMD) is caused by mutations in the gene encoding the nuclear membrane protein emerin (X-linked EDMD) or in the gene encoding lamins A/C (autosomal dominant EDMD). One hypothesis explaining the disease suggests that the mutations lead to weakness of the nuclear lamina. To test this hypothesis we investigated lamin solubility and distribution in skin fibroblasts from X-EDMD patients. Using in situ extraction of cells and immunofluorescence microscopy or biochemical fractionation and immunoblotting, we found that all lamin subtypes displayed increased solubility properties in fibroblasts from X-EDMD patients compared to normal individuals. Lamin and emerin solubility was mildly increased in fibroblasts from an X-EDMD carrier. Biochemical fractionation and immunoblotting also indicated that lamin C but no other lamin became redistributed from the nuclear lamina to the nucleoplasm in X-EDMD fibroblasts. Indirect immunofluorescence and confocal microscopy studies using lamin A- and lamin C-specific antibodies confirmed that lamin C but not lamin A became redistributed to the nucleoplasm. Interestingly, the lamin A/C binding protein LAP2α was also mislocalized in X-EDMD fibroblasts.

Citation

Markiewicz, E., Venables, R., Alvarez-Reyes, M., Quinlan, R., Dorobek, M., Hausmanowa-Petrusewicz, I., & Hutchison, C. (2002). Increased solubility of lamins and redistribution of lamin C in X-linked Emery Dreifuss Muscular Dystrophy Fibroblasts. Journal of Structural Biology, 140(1-3), 241-253. https://doi.org/10.1016/s1047-8477%2802%2900573-7

Journal Article Type Article
Publication Date Oct 1, 2002
Deposit Date May 17, 2007
Journal Journal of Structural Biology
Print ISSN 1047-8477
Electronic ISSN 1095-8657
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 140
Issue 1-3
Pages 241-253
DOI https://doi.org/10.1016/s1047-8477%2802%2900573-7
Keywords Emery-Dreifuss muscular dystrophy, lamin A/C, Emerin, Lamina-associated polypeptides, Nuclear envelope, Nuclear lamina.

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