SAD: A presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release
SAD: A presynaptic kinase associated with synaptic vesicles and the active zone cytomatrix that regulates neurotransmitter release
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DOI：
10.1016/j.neuron.2006.03.018
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发表时间：
2006-04-20
期刊：
影响因子：
16.2
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Inoue, E;Mochida, S;Takai, Y
在C. elegans调节突触发育。我们在这里报告的SAD-1，命名为SAD-A和SAD-B，这是专门在大脑中表达的哺乳动物直系同源物的分离和表征。SAD-B与突触囊泡相关，并且像活性区蛋白CAST和巴松管一样，与神经末梢中的突触前细胞基质紧密相关。SAD-B的突触定位需要COOH末端的短保守区（SCR）。在培养的大鼠海马神经元中，SAD-B的过表达显著增加了兴奋性突触后电流的频率，但其幅度并不显著。将SCR引入培养的突触上级颈上神经节神经元中显著抑制诱发性突触传递。此外，SCR降低了通过应用高渗蔗糖测量的易释放池的大小。此外，SAD-B磷酸化活性区蛋白RIM 1，但不是Munc 13 -1。这些结果表明，哺乳动物SAD激酶突触前调节神经递质的释放。
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.