HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Lamins A and C are differentially dysfunctional in autosomal dominant Emery-Dreifuss muscular dystrophy.

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.
AuthorsIsabell Motsch, Manuja Kaluarachchi, Lindsay J Emerson, Charlotte A Brown, Susan C Brown, Marie-Christine Dabauvalle, Juliet A Ellis
JournalEuropean journal of cell biology (Eur J Cell Biol) Vol. 84 Issue 9 Pg. 765-81 (Sep 2005) ISSN: 0171-9335 [Print] Germany
PMID16218190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: