Abstract |
Mutations in the LMNA gene, which encodes nuclear lamins A and C by alternative splicing, can give rise to Emery-Dreifuss muscular dystrophy. The mechanism by which lamins A and C separately contribute to this molecular phenotype is unknown. To address this question we examined ten LMNA mutations exogenously expressed as lamins A and C in COS-7 cells. Eight of the mutations when expressed in lamin A, exhibited a range of nuclear mislocalisation patterns. However, two mutations (T150P and delQ355) almost completely relocated exogenous lamin A from the nuclear envelope to the cytoplasm, disrupted nuclear envelope reassembly following cell division and altered the protein composition of the mid-body. In contrast, exogenously expressed DsRed2-tagged mutant lamin C constructs were only inserted into the nuclear lamina if co-expressed with any EGFP-tagged lamin A construct, except with one carrying the T150P mutation. The T150P, R527P and L530P mutations reduced the ability of lamin A, but not lamin C from binding to emerin. These data identify specific functional roles for the emerin- lamin C- and emerin- lamin A- containing protein complexes and is the first report to suggest that the A-type lamin mutations may be differentially dysfunctional for the same LMNA mutation.
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Authors | Isabell Motsch, Manuja Kaluarachchi, Lindsay J Emerson, Charlotte A Brown, Susan C Brown, Marie-Christine Dabauvalle, Juliet A Ellis |
Journal | European journal of cell biology
(Eur J Cell Biol)
Vol. 84
Issue 9
Pg. 765-81
(Sep 2005)
ISSN: 0171-9335 [Print] Germany |
PMID | 16218190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- Lamin Type A
- Membrane Proteins
- Nuclear Proteins
- Recombinant Fusion Proteins
- Thymopoietins
- emerin
- enhanced green fluorescent protein
- lamin C
- Green Fluorescent Proteins
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Topics |
- Animals
- COS Cells
- DNA, Complementary
(genetics)
- Green Fluorescent Proteins
(genetics, metabolism)
- Lamin Type A
(genetics)
- Membrane Proteins
(genetics, metabolism)
- Microscopy, Fluorescence
- Muscular Dystrophy, Emery-Dreifuss
(metabolism)
- Mutation
- Nuclear Lamina
(metabolism)
- Nuclear Proteins
- Recombinant Fusion Proteins
(genetics, metabolism)
- Thymopoietins
(genetics, metabolism)
- Transfection
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