Lamins A and C are differentially dysfunctional in autosomal dominant Emery-Dreifuss muscular dystrophy |
| |
Authors: | Motsch Isabell Kaluarachchi Manuja Emerson Lindsay J Brown Charlotte A Brown Susan C Dabauvalle Marie-Christine Ellis Juliet A |
| |
Institution: | The Randall Division of Cell and Molecular Biophysics, Kings College, New Hunts House, Guy's Campus, London SE1 1UL, UK. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|