Cbln1 Is a Ligand for an Orphan Glutamate Receptor δ2, a Bidirectional Synapse Organizer
Cbln1 Is a Ligand for an Orphan Glutamate Receptor δ2, a Bidirectional Synapse Organizer
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DOI：
10.1126/science.1185152
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发表时间：
2010-04-16
期刊：
影响因子：
56.9
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Matsuda, Keiko;Miura, Eriko;Yuzaki, Michisuke
小脑颗粒细胞分泌的 Cbln1 和浦肯野细胞表达的孤儿谷氨酸受体 delta 2 (GluD2) 对于成年小鼠这些神经元之间的突触完整性至关重要。然而，尚未鉴定出这些分子的内源结合配偶体。我们发现 Cbln1 直接与 GluD2 的 N 端结构域结合。突触后细胞表达的 GluD2 与外源应用的 Cbln1 相结合，对于在体外和体内成人小脑中诱导新突触是必要且充分的。此外，涂有重组 Cbln1 的珠子直接诱导突触前分化，并通过 GluD2 间接引起突触后分子聚集。这些结果表明 Cbln1-GluD2 复合物是一种独特的突触组织者，可双向作用于突触前和突触后成分。
Cbln1, secreted from cerebellar granule cells, and the orphan glutamate receptor delta 2 (GluD2), expressed by Purkinje cells, are essential for synapse integrity between these neurons in adult mice. Nevertheless, no endogenous binding partners for these molecules have been identified. We found that Cbln1 binds directly to the N-terminal domain of GluD2. GluD2 expression by postsynaptic cells, combined with exogenously applied Cbln1, was necessary and sufficient to induce new synapses in vitro and in the adult cerebellum in vivo. Further, beads coated with recombinant Cbln1 directly induced presynaptic differentiation and indirectly caused clustering of postsynaptic molecules via GluD2. These results indicate that the Cbln1-GluD2 complex is a unique synapse organizer that acts bidirectionally on both pre- and postsynaptic components.