Localization of fused in sarcoma (FUS) protein to the post-synaptic density in the brain
Localization of fused in sarcoma (FUS) protein to the post-synaptic density in the brain
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DOI：
10.1007/s00401-012-0984-6
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发表时间：
2012-09-01
影响因子：
12.7
通讯作者：
Akiyama, Haruhiko
中科院分区：
文献类型：
--
作者：
Aoki, Naoya;Higashi, Shinji;Akiyama, Haruhiko
肉瘤融合基因（FUS）的突变与家族性肌萎缩侧索硬化症（ALS）的一种形式ALS 6有关。FUS蛋白是ALS 6和一些罕见形式的额颞叶变性（FTLD）中泛素阳性神经元胞质内含物的主要成分。后者现在统称为FTLD-FUS。在本研究中，我们研究了FUS在人类和小鼠大脑中的定位。FUS通过蛋白质印迹法检测为人和小鼠脑中的约72 kDa蛋白质。免疫组织化学使用轻微固定的组织切片的人类和小鼠的大脑揭示了FUS阳性颗粒染色的神经胶质细胞，除了核染色。这种颗粒在脑干和脊髓的灰质中大量存在。它们在端脑中不常见。在光镜下，FUS阳性颗粒通常与突触素共同定位，并与微管相关蛋白2阳性树突共同存在。在小鼠脑的突触体部分中，FUS主要在突触后密度部分中检测到。因此，虽然FUS主要是一种核蛋白，但它也可能在树突中发挥作用。在伴有TDP-43沉积的FTLD患者（FTLD-TDP）的脑中，与对照病例相比，皮质中FUS阳性颗粒的数量增加。阿尔茨海默病（AD）的增加不那么显著，但仍然很重要。FUS的树突状定位及其在FTLD-TDP和AD中的增加可能对神经退行性疾病的病理生理学具有一定意义。
Mutations in the fused in sarcoma (FUS) gene are linked to a form of familial amyotrophic lateral sclerosis (ALS), ALS6. The FUS protein is a major component of the ubiquitin-positive neuronal cytoplasmic inclusions in both ALS6 and some rare forms of frontotemporal lobar degeneration (FTLD). The latter are now collectively referred to as FTLD-FUS. In the present study, we investigated the localization of FUS in human and mouse brains. FUS was detected by western blot as an approximately 72 kDa protein in both human and mouse brains. Immunohistochemistry using lightly fixed tissue sections of human and mouse brains revealed FUS-positive granular staining in the neuropil, in addition to nuclear staining. Such granules are abundant in the gray matter of the brainstem and spinal cord. They are not frequent in the telencephalon. At the light microscopic level, FUS-positive granules are often co-localized with synaptophysin and present in association with microtubule-associated protein 2-positive dendrites. In the synaptosomal fraction of mouse brain, FUS is detected mainly in the post-synaptic density fraction. Thus, while FUS is primarily a nuclear protein, it may also play a role in dendrites. In the brains of patients with FTLD with TDP-43 deposition (FTLD-TDP), the number of FUS-positive granules in the cortex is increased compared with control cases. The increase in Alzheimer's disease (AD) is less remarkable but still significant. The dendritic localization of FUS and its increase in FTLD-TDP and AD may have some implication for the pathophysiology of neurodegenerative diseases.