Department of Neurophysiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Cerebellum. 2012 Mar;11(1):78-84. doi: 10.1007/s12311-010-0186-5.
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 δ2 (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.
脑蛋白 11 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 precerebellin（Cbln1）在小脑颗粒细胞中产生。越来越明显的是，尽管脑蛋白可能具有某些功能，但 Cbln1 实际上是一种信号分子，属于 C1q 家族。然而，Cbln1 的精确功能仍未解决。Cbln1 从小脑颗粒细胞中释放出来，而 Cbln1 基因在小鼠中的破坏会导致浦肯野细胞与平行纤维（颗粒细胞的轴突）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 δ2（GluD2）在与平行纤维形成突触的浦肯野细胞树突棘上高度表达。尽管 GluD2 在 15 多年前就被确定为离子型谷氨酸受体的成员，但由于其内源性配体不清楚，因此被称为孤儿受体。有趣的是，GluD2 基因缺失小鼠与 cbln1 基因缺失小鼠的表型完全相同。因此，Cbln1 和 GluD2 被认为参与了形成平行纤维突触所需的共同信号通路。我们最近在 Cbln1 和 GluD2 之间建立了直接的配体-受体关系。Cbln1-GluD2 复合物位于平行纤维-浦肯野细胞突触的裂脑蛋白中，双向调节突触前和突触后分化。
