Inoue Eiji, Mochida Sumiko, Takagi Hiroshi, Higa Susumu, Deguchi-Tawarada Maki, Takao-Rikitsu Etsuko, Inoue Marie, Yao Ikuko, Takeuchi Kosei, Kitajima Isao, Setou Mitsutoshi, Ohtsuka Toshihisa, Takai Yoshimi
KAN Research Institute, Kyoto 600-8815, Japan.
Neuron. 2006 Apr 20;50(2):261-75. doi: 10.1016/j.neuron.2006.03.018.
A serine/threonine kinase SAD-1 in C. elegans regulates synapse development. We report here the isolation and characterization of mammalian orthologs of SAD-1, named SAD-A and SAD-B, which are specifically expressed in the brain. SAD-B is associated with synaptic vesicles and, like the active zone proteins CAST and Bassoon, is tightly associated with the presynaptic cytomatrix in nerve terminals. A short conserved region (SCR) in the COOH-terminus is required for the synaptic localization of SAD-B. Overexpression of SAD-B in cultured rat hippocampal neurons significantly increases the frequency of miniature excitatory postsynaptic current but not its amplitude. Introduction of SCR into presynaptic superior cervical ganglion neurons in culture significantly inhibits evoked synaptic transmission. Moreover, SCR decreases the size of the readily releasable pool measured by applying hypertonic sucrose. Furthermore, SAD-B phosphorylates the active zone protein RIM1 but not Munc13-1. These results suggest that mammalian SAD kinase presynaptically regulates neurotransmitter release.
秀丽隐杆线虫中的丝氨酸/苏氨酸激酶SAD-1调控突触发育。我们在此报告了SAD-1的哺乳动物直系同源物SAD-A和SAD-B的分离与特性，它们在大脑中特异性表达。SAD-B与突触小泡相关，并且像活性区蛋白CAST和巴松管一样，与神经末梢的突触前细胞骨架紧密相连。SAD-B的突触定位需要COOH末端的一个短保守区域（SCR）。在培养的大鼠海马神经元中过表达SAD-B可显著增加微小兴奋性突触后电流的频率，但不增加其幅度。将SCR导入培养的突触前颈上神经节神经元可显著抑制诱发的突触传递。此外，SCR可减小通过应用高渗蔗糖测量的易释放池的大小。此外，SAD-B可磷酸化活性区蛋白RIM1，但不能磷酸化Munc13-1。这些结果表明，哺乳动物SAD激酶在突触前调节神经递质释放。
