Cbln家族蛋白在突触形成中发挥功能的机制研究

神经系统发育过程中，神经突触的形成非常重要，但突触形成的分子机制还不清楚。近几年，Mishina和Yuzaki研究组发现小脑肽前体蛋白（Cerebellin 1 precursor protein，Cbln1）参与突触形成。Cbln1以六聚体形式存在，与含S4剪切片段的Neurexin蛋白（NRXN）和GluRδ2相互作用，介导小脑 颗粒细胞的平行纤维（PF）与Purkinje细胞（PC）之间突触的形成及维持。Cbln家族中，Cbln2同样介导NRXN蛋白与GluRδ家族蛋白间的相互作用；Cbln3则通过与Cbln1形成异源六聚体发挥功能；而Cbln4选择性地和神经突起诱向因子Netrin的受体DCC结合。对Cbln家族成员的结构与功能研究将揭示Cbln家族不同成员间的异同，阐释Cbln1以及Cbln2和NRXN蛋白相互作用的结构基础，并有助于深入了解PF-PC突触的形成及维持机制。

Synaptogenesis is critical for the development of the nervous system. However, the mechanisms underlying synaptogenesis and the dynamics of the associated signal transduction are still unclear. Recently, the Mishina and Yuzaki groups found that cerebellin 1 precursor protein (Cbln1) is a key factor in the formation and maintenance of synapses between parallel fibers (PFs) of cerebellum granule cells and Purkinje cells (PCs) in the cerebellum. Cbln1 exists as a hexamer and bridges the pre-synaptic neurexin proteins (NRXNs) containing the S4 splcing insert and post-synaptic GluRδ2 to form a trans-synaptic triad. Among the Cbln family members, Cbln2 plays a similar role, however, with lower affinities for NRXNs, GluRδ1 or GluRδ2. Cbln3 forms a heterogeneous hexamer with Cbln1 to exert its function, while Cbln4 selectively binds to the netrin receptor DCC. The structural and functional studies of Cbln family proteins will reveal their similarities and differences, identify the structural bases for the selective interactions of Cbln1 and Cbln2 with NRXN proteins, and elucidate the molecular mechanisms underlying the formation and maintenance of the PF-PC synapses.