The ESCRT-deubiquitinating enzyme USP8 in the cervical spinal cord of wild-type and Vps54-recessive (wobbler) mutant mice
The ESCRT-deubiquitinating enzyme USP8 in the cervical spinal cord of wild-type and Vps54-recessive (wobbler) mutant mice
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DOI：
10.1007/s00418-013-1096-7
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发表时间：
2014-01-01
影响因子：
2.3
通讯作者：
Berruti, Giovanna
中科院分区：
文献类型：
--
作者：
Paiardi, Chiara;Pasini, Maria Enrica;Berruti, Giovanna
Usp 8是一种去泛素化酶，作为内体运输的调节剂起作用，并参与细胞增殖。“体内”USP 8主要在中枢神经系统和睾丸中表达，这两个器官具有高度极化的细胞。考虑到神经元细胞功能严格依赖于囊泡运输和内吞货物的泛素介导的分选，研究神经元细胞，特别是运动神经元中的USP 8可能是相关的。在本研究中，我们发现USP 8在脊髓的灰质和白色物质中表达，标记神经元细胞体、轴突微管和突触终末。神经胶质成分基本上是USP 8免疫阴性的。运动神经元中USP 8与EEA 1的部分共定位表明USP 8参与早期内体运输，而与Vps 54的部分共定位表明参与逆行运输。变异Vps 54（L967 Q）是导致摇摆表型的原因，这是一种以运动神经元变性为特征的疾病。我们在wobbler脊髓中搜索USP 8/Vps 54。最值得一提的结果是，与野生型相比，摇摆少突胶质细胞具有强烈的USP 8免疫反应性;关于突变的Vps 54的细胞表达没有明显的改变。另一方面，至于神经元细胞内定位，USP 8和Vps 54（L967 Q）均未显示典型的点状分布，但似乎聚集在蛋白质聚集体中。总的来说，我们的研究表明，在神经元细胞中，USP 8可能参与内体运输，逆行运输和突触可塑性。在导致神经变性的疾病中，USP 8上调并可能影响神经元-少突胶质细胞相互作用。
Usp8 is a deubiquitinating enzyme that works as regulator of endosomal trafficking and is involved in cell proliferation. "In vivo" USP8 is predominantly expressed in the central nervous system and testis, two organs with highly polarized cells. Considering that neuronal cell functionality is strictly dependent on vesicular traffic and ubiquitin-mediated sorting of the endocytosed cargo, it could be of relevance to investigate about USP8 in neuronal cells, in particular motor neurons. In this study, we found that USP8 is expressed in the gray and white matter of the spinal cord, labeling neuronal cell bodies, axonal microtubules and synaptic terminals. The glia component is essentially USP8-immunonegative. The partial colocalization of USP8 with EEA1 in motor neurons indicates that USP8 is involved in early endosomal trafficking while that with Vps54 suggests an involvement in the retrograde traffic. The variant Vps54(L967Q) is responsible for the wobbler phenotype, a disorder characterized by motor neuron degeneration. We searched for USP8/Vps54 in wobbler spinal cord. The most worth-mention result was that wobbler oligodendrocytes, in contrast to the wild-type, are heavily USP8-immunoreactive; no significant modification was appreciated about the cellular expression of mutated Vps54. On the other hand, as to the neuronal intracellular localization, both USP8 and Vps54(L967Q) did not show the typical spot-like distribution, but seemed to accumulate in proteinaceous aggregates. Collectively, our study suggests that in neuronal cells USP8 could be involved in endosomal trafficking, retrograde transport and synaptic plasticity. In disorders leading to neurodegeneration USP8 is upregulated and could influence the neuron-oligodendrocyte interactions.