Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity.
Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity.
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DOI：
10.1016/j.mcn.2008.07.028
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发表时间：
2008-12
影响因子：
3.5
通讯作者：
Wilson, S. M.
中科院分区：
文献类型：
--
作者：
Walters, B. J.;Campbell, S. L.;Chen, P. C.;Taylor, A. P.;Schroeder, D. G.;Dobrunz, L. E.;Artavanis-Tsakonas, K.;Ploegh, H. L.;Wilson, J. A.;Cox, G. A.;Wilson, S. M.
泛素蛋白酶体途径与许多神经退行性疾病的发病机制有关，两种不同的去泛素化酶 Uch-L1 和 Usp14 的改变会导致小鼠的神经表型。我们在 Uch-L1 中发现了一个新的突变，并比较了 Uch-L1 和 Usp14 在泛素蛋白酶体系统中的作用。 Uch-L1 或 Usp14 的缺陷会导致泛素水平下降，这表明它们都调节神经系统中泛素的稳定性。然而，泛素耗尽对 Usp14 缺陷小鼠的生存能力和症状发作的影响更为严重，并且仅在 Usp14 缺陷小鼠中观察到海马突触传递的变化。此外，虽然 Usp14 似乎在蛋白酶体上发挥作用，但 Uch-L1 缺陷导致溶酶体成分上调，表明 Uch-L1 和 Usp14 可能通过调节细胞中不同的泛素池，对泛素蛋白酶体系统和突触活性产生不同的影响。
The ubiquitin proteasome pathway has been implicated in the pathogenesis of many neurodegenerative diseases, and alterations in two different deubiquitinating enzymes, Uch-L1 and Usp14, result in neurological phenotypes in mice. We identified a new mutation in Uch-L1 and compared the roles of Uch-L1 and Usp14 in the ubiquitin proteasome system. Deficiencies in either Uch-L1 or Usp14 result in decreased levels of ubiquitin, suggesting that they both regulate ubiquitin stability in the nervous system. However, the effect of ubiquitin depletion on viability and onset of symptoms is more severe in the Usp14-deficient mice, and changes in hippocampal synaptic transmission were only observed in Usp14-deficient mice. In addition, while Usp14 appears to function at the proteasome, Uch-L1 deficiency resulted in up-regulation of lysosomal components, indicating that Uch-L1 and Usp14 may differentially affect the ubiquitin proteasome system and synaptic activity by regulating different pools of ubiquitin in the cell.
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