The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells
The Secreted Protein C1QL1 and Its Receptor BAI3 Control the Synaptic Connectivity of Excitatory Inputs Converging on Cerebellar Purkinje Cells
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DOI：
10.1016/j.celrep.2015.01.034
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发表时间：
2015-02-10
期刊：
影响因子：
8.8
通讯作者：
Selimi, Fekrije
中科院分区：
文献类型：
--
作者：
Sigoillot, Severine M.;Iyer, Keerthana;Selimi, Fekrije
在给定的靶神经元上，不同类型的传入建立了精确的连接模式，导致了明确定义和不重叠的突触区域。在数量、形态和亚细胞定位方面，是什么调节了每种类型突触的特定特征，仍有待了解。在这里，我们证明了由分泌的补体C1q相关蛋白C1QL1及其受体黏附-GPCR脑血管生成抑制物3(BAI3)形成的信号通路控制着由兴奋性传入建立在小脑浦肯野细胞上的连接的刻板模式。BAI3受体调节平行纤维和攀升纤维传入的突触发生。其配体C1QL1在下橄榄核神经元中的有限和及时表达确保了攀援纤维的适当突触区域的建立。鉴于C1QL和BAI蛋白在发育中的小鼠脑中广泛表达，我们的研究揭示了有助于形成功能脑的一般机制。
Precise patterns of connectivity are established by different types of afferents on a given target neuron, leading to well-defined and non-overlapping synaptic territories. What regulates the specific characteristics of each type of synapse, in terms of number, morphology, and subcellular localization, remains to be understood. Here, we show that the signaling pathway formed by the secreted complement C1Q-related protein C1QL1 and its receptor, the adhesion- GPCR brain angiogenesis inhibitor 3 (BAI3), controls the stereotyped pattern of connectivity established by excitatory afferents on cerebellar Purkinje cells. The BAI3 receptor modulates synap-togenesis of both parallel fiber and climbing fiber afferents. The restricted and timely expression of its ligand C1QL1 in inferior olivary neurons ensures the establishment of the proper synaptic territory for climbing fibers. Given the broad expression of C1QL and BAI proteins in the developing mouse brain, our study reveals a general mechanism contributing to the formation of a functional brain.