Department of Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, 38163.
J Comp Neurol. 2014 Feb 1;522(2):479-97. doi: 10.1002/cne.23422.
The cerebellins (Cblns) are a family of secreted proteins that are widely expressed throughout the nervous system, but whose functions have been studied only in the cerebellum and striatum. Two members of the family, Cbln1 and Cbln2, bind to neurexins on presynaptic terminals and to GluRδs postsynaptically, forming trans-synaptic triads that promote synapse formation. Cbln1 has a higher binding affinity for GluRδs and exhibits greater synaptogenic activity than Cbln2. In contrast, Cbln4 does not form such triads and its function is unknown. The different properties of the three Cblns suggest that each plays a distinct role in synapse formation. To begin to elucidate Cbln function in other neuronal systems, we used in situ hybridization to examine Cbln expression in the mouse spinal cord. We find that neurons expressing Cblns 1, 2, and 4 tend to occupy different laminar positions within the dorsal spinal cord, and that Cbln expression is limited almost exclusively to excitatory neurons. Combined in situ hybridization and immunofluorescent staining shows that Cblns 1, 2, and 4 are expressed by largely distinct neuronal subpopulations, defined in part by sensory input, although there is some overlap and some individual neurons coexpress two Cblns. Our results suggest that differences in connectivity between subpopulations of dorsal spinal cord neurons may be influenced by which Cbln each subpopulation contains. Competitive interactions between axon terminals may determine the number of synapses each forms in any given region, and thereby contribute to the development of precise patterns of connectivity in the dorsal gray matter.
小脑蛋白（Cblns）是一组广泛表达于神经系统的分泌蛋白，但其功能仅在小脑和纹状体中得到研究。该家族的两个成员，Cbln1 和 Cbln2，与突触前末梢的神经连接蛋白结合，并与突触后 GluRδ 结合，形成促进突触形成的跨突触三联体。Cbln1 与 GluRδ 的结合亲和力更高，其促突触生成活性也高于 Cbln2。相比之下，Cbln4 不形成这种三联体，其功能未知。三种 Cblns 的不同特性表明它们各自在突触形成中发挥着独特的作用。为了开始阐明 Cbln 在其他神经元系统中的功能，我们使用原位杂交技术研究了 Cbln 在小鼠脊髓中的表达。我们发现，表达 Cblns 1、2 和 4 的神经元倾向于占据脊髓背侧的不同层位，并且 Cbln 的表达几乎完全局限于兴奋性神经元。结合原位杂交和免疫荧光染色显示，Cblns 1、2 和 4 主要由不同的神经元亚群表达，部分由感觉输入定义，尽管存在一些重叠，并且一些单个神经元共表达两种 Cbln。我们的结果表明，背侧脊髓神经元亚群之间的连接差异可能受到每个亚群包含的 Cbln 影响。轴突末梢之间的竞争相互作用可能决定每个末梢在任何特定区域形成的突触数量，从而有助于在背侧灰质中形成精确的连接模式。
