Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis.
Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis.
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DOI：
10.1091/mbc.e11-06-0505
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发表时间：
2012-02
影响因子：
3.3
通讯作者：
Gruenbaum Y
中科院分区：
文献类型：
--
作者：
Barkan R;Zahand AJ;Sharabi K;Lamm AT;Feinstein N;Haithcock E;Wilson KL;Liu J;Gruenbaum Y
ETOC：缺乏Ce-emerin和LEM-2的秀丽隐杆线虫表明，这些蛋白质对于特定谱系的发育、体细胞的有丝分裂和平滑肌活性是必需的。LEM-2缺失蠕虫的寿命缩短和平滑肌活性降低预测人类LEM 2基因与比Emery-Dreifuss肌营养不良症更严重的疾病有关。Emerin和LEM 2是从人类到秀丽隐杆线虫保守的普遍存在的内核膜蛋白。人类Emerin的缺失导致Emery-Dreifuss肌营养不良症（EDMD）。为了测试emerin和LEM 2在体细胞中的作用，我们使用这两个基因的无效等位基因来产生C。elegans动物是亚型的（LEM-2-缺失和Ce-emerin杂合）或两种蛋白质都缺失。单零和亚型动物是可行的和可生育的。双无效动物使用Ce-emerin的母体池发育至幼虫L2期，然后停止。非分裂体细胞核正常，而分裂细胞异常核膜和染色质组织和严重缺陷的胚后细胞分裂，包括中胚层谱系。寿命不受单独Ce-emerin损失的影响，但在LEM-2缺失动物中显着减少，而双缺失动物的寿命甚至更短。除了横纹肌缺陷之外，双缺失动物和LEM-2缺失动物显示出平滑肌活性的意外缺陷。这些发现暗示人类LEM 2突变是EDMD的潜在原因，并进一步表明人类LEM 2突变可能导致更严重的不同疾病，因为C.仅缺乏LEM-2的秀丽线虫具有显著降低的寿命和平滑肌活性。
ETOC: Caenorhabditis elegans lacking both Ce-emerin and LEM-2 show that these proteins are essential for development of specific lineages, mitosis in somatic cells, and smooth muscle activity. Reduced life span and smooth muscle activity of LEM-2–null worms predicts human LEM2 gene links to diseases more severe than Emery-Dreifuss muscular dystrophy. 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.