eEF1A2 and neuronal degeneration
eEF1A2 and neuronal degeneration
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DOI：
10.1042/bst0371293
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发表时间：
2009-12-01
影响因子：
3.9
通讯作者：
Soares, Dinesh C.
中科院分区：
文献类型：
--
作者：
Abbott, Catherine M.;Newbery, Helen J.;Soares, Dinesh C.
翻译延伸因子eEF 1A（真核细胞延伸因子1A）在哺乳动物中以两种单独编码的变体存在，它们在氨基酸水平上98%相似，92%相同。一种变体eEF 1A 1几乎普遍表达，另一种变体eEF 1A 2显示出非常有限的表达模式。1972年描述了一种自发突变，它产生了浪费表型：纯合子wst/wst小鼠正常发育，直到断奶后不久，但随后失去肌肉体积，获得震颤和步态异常，并在4周内死亡。该突变已被证明是15 kb的缺失，其去除了编码eEF 1A 2的基因的启动子和第一外显子。肌肉中eEF 1A 1和eEF 1A 2表达的相互模式与消瘦小鼠表型发作的时间非常吻合：eEF 1A 1在出生后下降，直到3周时检测不到，而eEF 1A 2表达在此期间增加。在浪费的缺失中不存在其他基因，转基因研究表明，表型是由于eEF 1A 2的丢失。我们已经表明，eEF 1A 2，而不是eEF 1A 1，也表达在高水平的运动神经元在脊髓。消瘦的小鼠发展出运动神经元变性的许多病理学特征，并且可以代表运动神经元疾病早期发作的良好模型。eEF 1A 1和eEF 1A 2蛋白质结构的分子建模突出了两种变体之间的差异，这可能是功能差异的关键。eEF 1A 2和ZPR 1（锌指蛋白1）之间的相互作用，其与SMN（运动神经元存活）蛋白相互作用，在运动神经元生物学中可能是重要的。
Translation elongation factor eEF1A (eukaryotic elongation factor 1A) exists as two individually encoded variants in mammals, which are 98% similar and 92% identical at the amino acid level. one variant, eEF1A1, is almost ubiquitously expressed, the other variant, eEF1A2, shows a very restricted pattern of expression. A spontaneous mutation was described in 1972, which gives rise to the wasted phenotype: homozygous wst/wst mice develop normally until shortly after weaning, but then lose muscle bulk, acquire tremors and gait abnormalities and die by 4 weeks. This mutation has been shown to be a deletion of 15 kb that removes the promoter and first exon of the gene encoding eEF1A2. The reciprocal pattern of expression of eEF1A1 and eEF1A2 in muscle fits well with the timing of onset of the phenotype of wasted mice: eEF1A1 declines after birth until it is undetectable by 3 weeks, whereas eEF1A2 expression increases over this time. No other gene is present in the wasted deletion, and transgenic studies have shown that the phenotype is due to loss of eEF1A2. We have shown that eEF1A2, but not eEF1A1, is also expressed at high levels in motor neurons in the spinal cord. wasted mice develop many pathological features of motor neuron degeneration and may represent a good model for early onset of motor neuron disease. Molecular modelling of the eEF1A1 and eEF1A2 protein structures highlights differences between the two variants that may be critical for functional differences. interactions between eEF1A2 and ZPR1 (zinc-finger protein 1), which interacts with the SMN (survival motor neuron) protein, may be important in motor neuron biology.