Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles.
Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles.
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DOI：
10.1523/jneurosci.0924-08.2008
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发表时间：
2008-10-22
期刊：
影响因子：
--
通讯作者：
Augustine GJ
中科院分区：
文献类型：
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作者：
Gitler D;Cheng Q;Greengard P;Augustine GJ
突触蛋白通过控制突触小泡的储备池来调节突触传递。三个哺乳动物突触蛋白基因中的每一个都会发生选择性剪接，产生几种作用未知的亚型。为了研究这些亚型的功能，我们检查了将每种亚型引入来自突触蛋白三重敲除小鼠的谷氨酸能培养的海马神经元中的突触效应。值得注意的是，我们发现突触蛋白 IIa 是唯一能够挽救三重敲除小鼠突触抑制表型的亚型；其他检查的异构体，包括经过充分研究的突触蛋白 Ia 异构体，对突触抑制的动力学没有显着影响。突触蛋白 IIa 对突触抑制的减缓与储备池突触小泡密度的增加在数量上是平行的，这可以通过囊泡蛋白 synaptobrevin-2 的荧光标记或通过苯乙烯基染料 FM4-64 染色来测量。我们的结果进一步支持了以下假设：突触蛋白通过控制囊泡储备库的大小来定义谷氨酸能突触突触抑制的动力学，并将突触蛋白 IIa 确定为主要负责此任务的亚型。
Synapsins regulate synaptic transmission by controlling the reserve pool of synaptic vesicles. Each of the three mammalian synapsin genes is subject to alternative splicing, yielding several isoforms whose roles are unknown. To investigate the function of these isoforms, we examined the synaptic effects of introducing each isoform into glutamatergic cultured hippocampal neurons from synapsin triple knock-out mice. Remarkably, we found that synapsin IIa was the only isoform that could rescue the synaptic depression phenotype of the triple knock-out mice; other isoforms examined, including the well-studied synapsin Ia isoform, had no significant effect on the kinetics of synaptic depression. The slowing of synaptic depression by synapsin IIa was quantitatively paralleled by an increase in the density of reserve pool synaptic vesicles, as measured either by fluorescent tagging of the vesicle protein synaptobrevin-2 or by staining with the styryl dye FM4-64. Our results provide further support for the hypothesis that synapsins define the kinetics of synaptic depression at glutamatergic synapses by controlling the size of the vesicular reserve pool and identify synapsin IIa as the isoform primarily responsible for this task.