| Autor: |
Sylvius N; Laboratory of Genetics of Cardiac Diseases, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Canada. sylvius@cng.fr, Hathaway A, Boudreau E, Gupta P, Labib S, Bolongo PM, Rippstein P, McBride H, Bilinska ZT, Tesson F |
| Jazyk: |
angličtina |
| Zdroj: |
Experimental cell research [Exp Cell Res] 2008 Aug 01; Vol. 314 (13), pp. 2362-75. Date of Electronic Publication: 2008 May 10. |
| DOI: |
10.1016/j.yexcr.2008.04.017 |
| Abstrakt: |
Mutations in the lamin A/C gene are involved in multiple human disorders for which the pathophysiological mechanisms are partially understood. Conflicting results prevail regarding the organization of lamin A and C mutants within the nuclear envelope (NE) and on the interactions of each lamin to its counterpart. We over-expressed various lamin A and C mutants both independently and together in COS7 cells. When expressed alone, lamin A with cardiac/muscular disorder mutations forms abnormal aggregates inside the NE and not inside the nucleoplasm. Conversely, the equivalent lamin C organizes as intranucleoplasmic aggregates that never connect to the NE as opposed to wild type lamin C. Interestingly, the lamin C molecules present within these aggregates exhibit an abnormal increased mobility. When co-expressed, the complex formed by lamin A/C aggregates in the NE. Lamin A and C mutants for lipodystrophy behave similarly to the wild type. These findings reveal that lamins A and C may be differentially affected depending on the mutation. This results in multiple possible physiological consequences which likely contribute in the phenotypic variability of laminopathies. The inability of lamin C mutants to join the nuclear rim in the absence of lamin A is a potential pathophysiological mechanism for laminopathies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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Full Text from ScienceDirect