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The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype.
J Cell Sci. 2002 Jan 15; 115(Pt 2):341-54.JC

Abstract

Emerin is the nuclear membrane protein defective in X-linked Emery-Dreifuss muscular dystrophy (X-EDMD). The majority of X-EDMD patients have no detectable emerin. However, there are cases that produce mutant forms of emerin, which can be used to study its function. Our previous studies have shown that the emerin mutants S54F, P183T, P183H, Del95-99, Del236-241 (identified in X-EDMD patients) are targeted to the nuclear membrane but to a lesser extent than wild-type emerin. In this paper, we have studied how the mislocalisation of these mutant emerins may affect nuclear functions associated with the cell cycle using flow cytometry and immunofluorescence microscopy. We have established that cells expressing the emerin mutant Del236-241 (a deletion in the transmembrane domain), which was mainly localised in the cytoplasm, exhibited an aberrant cell cycle length. Thereafter, by examining the intracellular localisation of endogenously expressed lamin A/C and exogenously expressed wild-type and mutant forms of emerin after a number of cell divisions, we determined that the mutant forms of emerin redistributed endogenous lamin A/C. The extent of lamin A/C redistribution correlated with the amount of EGFP-emerin that was mislocalised. The amount of EGFP-emerin mislocalized, in turn, was associated with alterations in the nuclear envelope morphology. The nuclear morphology and redistribution of lamin A/C was most severely affected in the cells expressing the emerin mutant Del236-241. It is believed that emerin is part of a novel nuclear protein complex consisting of the barrier-to-autointegration factor (BAF), the nuclear lamina, nuclear actin and other associated proteins. The data presented here show that lamin A/C localisation is dominantly directed by its interaction with certain emerin mutants and perhaps wild-type emerin as well. These results suggest that emerin links A-type lamins to the nuclear envelope and that the correct localisation of these nuclear proteins is important for maintaining cell cycle timing.

Authors+Show Affiliations

MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. ealf@mrc-lmb.cam.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11839786

Citation

Fairley, Elizabeth A L., et al. "The Cell Cycle Dependent Mislocalisation of Emerin May Contribute to the Emery-Dreifuss Muscular Dystrophy Phenotype." Journal of Cell Science, vol. 115, no. Pt 2, 2002, pp. 341-54.
Fairley EA, Riddell A, Ellis JA, et al. The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype. J Cell Sci. 2002;115(Pt 2):341-54.
Fairley, E. A., Riddell, A., Ellis, J. A., & Kendrick-Jones, J. (2002). The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype. Journal of Cell Science, 115(Pt 2), 341-54.
Fairley EA, et al. The Cell Cycle Dependent Mislocalisation of Emerin May Contribute to the Emery-Dreifuss Muscular Dystrophy Phenotype. J Cell Sci. 2002 Jan 15;115(Pt 2):341-54. PubMed PMID: 11839786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The cell cycle dependent mislocalisation of emerin may contribute to the Emery-Dreifuss muscular dystrophy phenotype. AU - Fairley,Elizabeth A L, AU - Riddell,Andrew, AU - Ellis,Juliet A, AU - Kendrick-Jones,John, PY - 2002/2/13/pubmed PY - 2002/5/3/medline PY - 2002/2/13/entrez SP - 341 EP - 54 JF - Journal of cell science JO - J Cell Sci VL - 115 IS - Pt 2 N2 - Emerin is the nuclear membrane protein defective in X-linked Emery-Dreifuss muscular dystrophy (X-EDMD). The majority of X-EDMD patients have no detectable emerin. However, there are cases that produce mutant forms of emerin, which can be used to study its function. Our previous studies have shown that the emerin mutants S54F, P183T, P183H, Del95-99, Del236-241 (identified in X-EDMD patients) are targeted to the nuclear membrane but to a lesser extent than wild-type emerin. In this paper, we have studied how the mislocalisation of these mutant emerins may affect nuclear functions associated with the cell cycle using flow cytometry and immunofluorescence microscopy. We have established that cells expressing the emerin mutant Del236-241 (a deletion in the transmembrane domain), which was mainly localised in the cytoplasm, exhibited an aberrant cell cycle length. Thereafter, by examining the intracellular localisation of endogenously expressed lamin A/C and exogenously expressed wild-type and mutant forms of emerin after a number of cell divisions, we determined that the mutant forms of emerin redistributed endogenous lamin A/C. The extent of lamin A/C redistribution correlated with the amount of EGFP-emerin that was mislocalised. The amount of EGFP-emerin mislocalized, in turn, was associated with alterations in the nuclear envelope morphology. The nuclear morphology and redistribution of lamin A/C was most severely affected in the cells expressing the emerin mutant Del236-241. It is believed that emerin is part of a novel nuclear protein complex consisting of the barrier-to-autointegration factor (BAF), the nuclear lamina, nuclear actin and other associated proteins. The data presented here show that lamin A/C localisation is dominantly directed by its interaction with certain emerin mutants and perhaps wild-type emerin as well. These results suggest that emerin links A-type lamins to the nuclear envelope and that the correct localisation of these nuclear proteins is important for maintaining cell cycle timing. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/11839786/The_cell_cycle_dependent_mislocalisation_of_emerin_may_contribute_to_the_Emery_Dreifuss_muscular_dystrophy_phenotype_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11839786 DB - PRIME DP - Unbound Medicine ER -