| RRC ID |
46022
|
| Author |
Barkan R, Zahand AJ, Sharabi K, Lamm AT, Feinstein N, Haithcock E, Wilson KL, Liu J, Gruenbaum Y.
|
| Title |
Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis.
|
| Journal |
Mol Biol Cell
|
| Abstract |
Emerin and LEM2 are ubiquitous inner nuclear membrane proteins conserved from humans to Caenorhabditis elegans. Loss of human emerin causes Emery-Dreifuss muscular dystrophy (EDMD). To test the roles of emerin and LEM2 in somatic cells, we used null alleles of both genes to generate C. elegans animals that were either hypomorphic (LEM-2-null and heterozygous for Ce-emerin) or null for both proteins. Single-null and hypomorphic animals were viable and fertile. Double-null animals used the maternal pool of Ce-emerin to develop to the larval L2 stage, then arrested. Nondividing somatic cell nuclei appeared normal, whereas dividing cells had abnormal nuclear envelope and chromatin organization and severe defects in postembryonic cell divisions, including the mesodermal lineage. Life span was unaffected by loss of Ce-emerin alone but was significantly reduced in LEM-2-null animals, and double-null animals had an even shorter life span. In addition to striated muscle defects, double-null animals and LEM-2-null animals showed unexpected defects in smooth muscle activity. These findings implicate human LEM2 mutations as a potential cause of EDMD and further suggest human LEM2 mutations might cause distinct disorders of greater severity, since C. elegans lacking only LEM-2 had significantly reduced life span and smooth muscle activity.
|
| Volume |
23(4)
|
| Pages |
543-52
|
| Published |
2012-2-1
|
| DOI |
10.1091/mbc.E11-06-0505
|
| PII |
mbc.E11-06-0505
|
| PMID |
22171324
|
| PMC |
PMC3279384
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / growth & development*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / physiology*
Cell Cycle Proteins
Cell Proliferation
Chromatin / metabolism
Chromatin / ultrastructure
Gene Deletion
Gene Expression Regulation, Developmental
Humans
Longevity / genetics
Membrane Proteins / genetics
Membrane Proteins / physiology*
Mesoderm / growth & development
Mesoderm / metabolism
Mitosis / genetics
Mitosis / physiology*
Muscle Contraction / genetics
Muscle Contraction / physiology
Muscle, Smooth / metabolism
Muscle, Smooth / physiology*
Muscle, Striated / metabolism
Muscle, Striated / physiology*
Muscular Dystrophy, Emery-Dreifuss / genetics
Mutation
Nuclear Envelope / metabolism
Nuclear Envelope / ultrastructure
Nuclear Proteins / genetics
Nuclear Proteins / physiology*
Sarcomeres / metabolism
Sarcomeres / physiology
Subcutaneous Tissue / growth & development
Subcutaneous Tissue / metabolism
|
| IF |
3.791
|
| Times Cited |
23
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1582 |
