Selective targeting of somatostatin receptor 3 to neuronal cilia

Selective targeting of somatostatin receptor 3 to neuronal cilia
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DOI:
10.1016/s0306-4522(98)00354-6
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发表时间:
1999-03-01
期刊:
影响因子:
3.3
通讯作者:
Höllt, V
Höllt, V
中科院分区:
医学3区
文献类型:
--
作者:
Händel, M;Schulz, S;Höllt, V

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最近,生长抑素受体家族的5个成员被克隆出来。然而,对它们在中枢神经系统中的细胞和亚细胞定位知之甚少。利用特异性抗肽抗血清,我们观察到生长抑素受体3样免疫反应在大脑皮层、海马、下丘脑、杏仁核和小脑等多个脑区。在所有这些区域(小脑皮层除外),生长抑素受体3样免疫反应选择性地靶向4-8 μ m长的杆状轮廓,这些轮廓与轴突或树突标记物不共定位。一个免疫反应谱总是与一个神经元细胞体相关。这种染色模式对秋水仙碱具有抗性,并与生长抑素受体3信使RNA紧密重叠分布,表明受体蛋白不会进行长距离运输。电镜分析显示,生长抑素受体3样免疫反应性局限于神经元纤毛的质膜,并延伸至细胞间袋,在其基体和近端段呈9+0丝状。因此,生长抑素受体3展示了一个独特的例子,即g蛋白偶联受体不局限于“经典的”突触前或突触后位点,而是选择性地靶向于神经元纤毛。生长抑素受体3受体在神经元纤毛上的存在表明,这些可能不运动的纤毛可能不仅仅代表发育残留物,而是作为直接环境的化学传感器起作用。(c) 1999年ibro。Elsevier Science Ltd.出版。
Recently, five members of the somatostatin receptor family have been cloned. However, little is known about their cellular and subcellular localization in the central nervous system. Using specific anti-peptide antisera, we observed somatostatin receptor 3-like immunoreactivity in many brain regions, including the cerebral cortex, hippocampus, hypothalamus, amygdala and cerebellum. In all of these regions (except for the cerebellar cortex), somatostatin receptor 3-like immunoreactivity was selectively targeted to 4-8-mu m-long rod-shaped profiles which did not co-localize with axonal or dendritic markers. One immunoreactive profile was always associated with one neuronal cell body. This staining pattern was resistant to colchicine treatment and showed a closely overlapping distribution with somatostatin receptor 3 messenger RNA, suggesting that the receptor protein is not transported over long distances. Electron microscopic analysis revealed that somatostatin receptor 3-like immunoreactivity is localized to the plasma membrane of neuronal cilia which extended into an intercellular pocket and showed a 9+0 filament pattern in their basal body and proximal segments.Thus, somatostatin receptor 3 demonstrates a unique example of a G-protein-coupled receptor not localized to "classical" pre- or postsynaptic sites, but selectively targeted to neuronal cilia. The presence of the somatostatin receptor 3 receptor on neuronal cilia suggests that these presumably non-motile cilia may not merely represent developmental remnants, but rather function as chemical sensors of the immediate milieu. (C) 1999 IBRO. Published by Elsevier Science Ltd.