Clustered protocadherins (Pcdhs) are a large family of ~60 cadherin-like proteins (divided into the subclasses α, β and γ) that compose a surface "barcode" in individual neurons. The code is generated through combinatorial expression via epigenetic regulation at a large gene cluster that encodes the molecules. During early neural development, Pcdhs were shown to mediate dendrite self-avoidance in some neuronal types through a still uncharacterized anti-adhesive mechanism. Pcdhs were also shown to be important for dendritic complexity in cortical neurons likely through a pro-adhesive mechanism. Pcdhs have also been postulated to participate in synaptogenesis and the specificity of connectivity. Some synaptic defects were noted in knockout animals, including synaptic number and physiology, but the role of these molecules in synaptic development is not understood. The effects of Pcdh knockout on dendritic patterning may present a confound to studying synaptogenesis. We have shown previously in vivo and in cultures that Pcdh-γs are highly enriched in intracellular compartments located in dendrites and spines with localization at only a few synaptic clefts. To gain insight into how Pcdh-γs might affect synapses, we compared synapses that harbored endogenous Pcdh-γs versus those that did not for parameters of synaptic maturation including pre- and postsynaptic size, postsynaptic perforations, and spine morphology by light microscopy in cultured hippocampal neurons and by serial section immuno-electron microscopy in hippocampal CA1. In mature neurons, synapses immunopositive for Pcdh-γs were found to be larger in diameter with more frequent perforations. Analysis of spines in cultured neurons revealed that mushroom spines were more frequently immunopositive for Pcdh-γs at their tips than thin spines. Taken together, these results suggest that Pcdh-γfunction at the synapse may be related to promotion of synaptic maturation and stabilization.

中文翻译：

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γ-procadcadherin在突触中的定位对应于突触成熟的参数

成簇的原钙粘蛋白（Pcdhs）是约60个钙粘蛋白样蛋白的大家族（分为亚类α，β和γ），它们构成单个神经元的表面“条形码”。该代码是通过在表观遗传的调控下，在编码该分子的大型基因簇上通过组合表达而产生的。在早期的神经发育过程中，Pcdhs被证明通过仍未表征的抗粘附机制介导某些神经元类型的树突自我回避。还显示，Pcdhs对于皮层神经元的树突复杂性很重要，这很可能是通过促粘附机制引起的。还假定Pcdhs参与突触发生和连接的特异性。在基因敲除动物中发现了一些突触缺陷，包括突触数量和生理学，但是尚不清楚这些分子在突触发育中的作用。Pcdh基因敲除对树突状图案的影响可能会困扰研究突触发生。我们以前已经在体内和文化中表明，Pcdh-γs在树突和棘突的细胞内区室中高度富集，仅定位在少数突触裂隙中。为了深入了解Pcdh-γs如何影响突触，我们通过光学显微镜在培养的海马体中比较了内源性Pcdh-γs与没有突触成熟参数（包括突触前和突触后大小，突触后穿孔和脊柱形态）的突触。神经元和海马CA1中的连续切片免疫电子显微镜检查。在成熟的神经元中 发现对Pcdh-γs免疫阳性的突触直径较大，且穿孔频繁。对培养的神经元中的棘进行分析后发现，蘑菇棘在其尖端比Psdh-γs的免疫阳性更高。综上所述，这些结果表明突触中的Pcdh-γ功能可能与促进突触成熟和稳定有关。