Cbln1 and the Delta2 Glutamate Receptor-An Orphan Ligand and an Orphan Receptor Find Their Partners
Cbln1 and the Delta2 Glutamate Receptor-An Orphan Ligand and an Orphan Receptor Find Their Partners
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DOI：
10.1007/s12311-010-0186-5
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发表时间：
2012-03-01
期刊：
影响因子：
3.5
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Matsuda, Keiko;Yuzaki, Michisuke
小脑蛋白最初是在二十多年前作为浦肯野细胞特异性肽被发现的。后来发现其前体蛋白前小脑蛋白（Cbln1）是在小脑颗粒细胞中产生的。越来越清楚的是，尽管小脑肽可能具有某些功能，但 Cbln1 是属于 C1q 家族的实际信号分子。然而，Cbln1的确切功能尚未解决。 Cbln1 由颗粒细胞释放，小鼠中 cbln1 基因的破坏会导致浦肯野细胞和平行纤维（PF；颗粒细胞轴突）之间的突触数量严重减少，并导致小脑共济失调。谷氨酸受体 delta 2 (GluD2) 在浦肯野细胞的树突棘上高度表达，树突棘与 PF 形成突触。尽管 GluD2 在 15 多年前就被鉴定为离子型谷氨酸受体的成员，但由于其内源性配体尚不清楚，因此被称为孤儿受体。有趣的是，GluD2 缺失小鼠的表型与 cbln1 缺失小鼠的表型完全相同。因此，Cbln1 和 GluD2 被认为参与 PF 突触形成所需的共同信号传导途径。我们最近在 Cbln1 和 GluD2 之间建立了直接的配体-受体关系。 Cbln1-GluD2 复合物位于 PF-浦肯野细胞突触间隙，双向调节突触前和突触后分化。
Cerebellin was originally discovered as a Purkinje cell-specific peptide more than two decades ago. Later, its precursor protein precerebellin (Cbln1) was found to be produced in cerebellar granule cells. It has become increasingly clear that although the cerebellin peptide may have certain functions, Cbln1 is an actual signaling molecule that belongs to the C1q family. However, the precise function of Cbln1 has been unresolved. Cbln1 is released from granule cells, and disruption of the cbln1 gene in mice causes a severe reduction in the number of synapses between Purkinje cells and parallel fibers (PFs; axons of granule cells) and results in cerebellar ataxia. The glutamate receptor delta 2 (GluD2) is highly expressed on Purkinje cells' dendritic spines which make synapses with PFs. Although GluD2 was identified as a member of the ionotropic glutamate receptors more than 15 years ago, it has been referred to as an orphan receptor because its endogenous ligands are unclear. Interestingly, GluD2-null mice phenocopy cbln1-null mice precisely. Cbln1 and GluD2 have therefore been thought to participate in a common signaling pathway that is required for the formation of PF synapses. We recently established a direct ligand-receptor relationship between Cbln1 and GluD2. The Cbln1-GluD2 complex is located at the cleft of PF-Purkinje cell synapses and bidirectionally regulates both presynaptic and postsynaptic differentiation.