Postsynaptic and differential localization to neuronal subtypes of protocadherin β16 in the mammalian central nervous system
Postsynaptic and differential localization to neuronal subtypes of protocadherin β16 in the mammalian central nervous system
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DOI：
10.1111/j.1460-9568.2008.06052.x
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Kemler, Rolf
中科院分区：
文献类型：
--
作者：
Junghans, Dirk;Heidenreich, Matthias;Kemler, Rolf
突触的形成依赖于促进正确识别、稳定和功能的表面粘附分子的表达。在人和小鼠中发现的 60 多种簇状原钙粘蛋白（Pcdh α、Pcdh β 和 Pcdh γ）因其簇状基因组组织以及 α-和 γ-Pcdh 在分配指定突触连接的神经元表面代码中的潜在作用而引起了相当大的关注。在这里，我们研究了 beta-Pcdhs 是否也有助于这些过程。通过进行 RT-PCR，我们发现许多 β-Pcdh 在神经发生开始时出现惊人的平行表达，并在中枢神经系统中广泛表达。我们生成了 Pcdhb16 特异性抗体，并显示 Pcdhb16 蛋白在成年小鼠小脑、海马和大脑皮层中的定位。详细分析小鼠视网膜揭示了 Pcdhb16 定位于特定细胞类型，更重要的是，定位于突触子集。我们发现 Pcdhb16 主要定位于突触后区室，与 Pcdhb22 的比较表明哺乳动物中枢神经系统中各个 β-Pcdh 的定位和功能存在差异。此外，我们还提供了 β-Pcdhs 在光感受器外节和连接纤毛中的作用的证据。我们的数据首次表明，β-Pcdhs 也定位于特定的神经元亚群和突触，这为以下假设提供了支持：聚集的 Pcdhs 是突触连接和神经元网络规范的候选基因。
The formation of synapses is dependent on the expression of surface adhesion molecules that facilitate correct recognition, stabilization and function. The more than 60 clustered protocadherins (Pcdh alpha, Pcdh beta and Pcdh gamma) identified in human and mouse have attracted considerable attention because of their clustered genomic organization and the potential role of alpha- and gamma-Pcdhs in allocating a neuronal surface code specifying synaptic connectivity. Here, we investigated whether beta-Pcdhs also contribute to these processes. By performing RT-PCR, we found a striking parallel onset of expression of many beta-Pcdhs around the onset of neurogenesis and wide expression in the central nervous system. We generated antibodies specific to Pcdhb16 and showed localization of Pcdhb16 protein in the adult mouse cerebellum, hippocampus and cerebral cortex. Analysing the mouse retina in detail revealed localization of Pcdhb16 to specific cell types and, importantly, subsets of synapses. We show that Pcdhb16 localizes predominantly to postsynaptic compartments and the comparison with Pcdhb22 implies differential localization and functions of individual beta-Pcdhs in the mammalian central nervous system. Moreover, we provide evidence for a role of beta-Pcdhs in the outer segments and connecting cilia of photoreceptors. Our data show for the first time that beta-Pcdhs also localize to specific neuronal subpopulations and synapses, providing support for the hypothesis that clustered Pcdhs are candidate genes for the specification of synaptic connectivity and neuronal networks.