A role for Mints in transmitter release:: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission
A role for Mints in transmitter release:: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission
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DOI：
10.1073/pnas.252774899
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发表时间：
2003-02-04
影响因子：
11.1
通讯作者：
Südhof, TC
中科院分区：
文献类型：
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作者：
Ho, A;Morishita, W;Südhof, TC
Mint（也称为X11样蛋白）是由不同的N-末端序列组成的衔接蛋白，其结合突触蛋白如CASK（仅Mint 1）和Munc 18 -1（Mint 1和2），保守的C-末端PTB-和PDZ-结构域结合广泛分布的蛋白质，如APP，早老素和Ca 2+通道（所有Mint）。我们发现，薄荷糖1和2类似地表达在大多数神经元中，除了抑制性中间神经元含有选择性高水平的薄荷糖1。使用基因敲除小鼠，我们表明，Mint 1的缺失不会损害生存或改变整体大脑结构，反对Mint 1-CASK复合物的基本发育功能。在海马的电生理记录中，我们没有观察到Mint 1缺陷小鼠兴奋性突触的短期或长期突触可塑性的变化，也没有检测到α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）与N-甲基-D-天冬氨酸（NMDA）受体介导的突触电流的比值发生变化。因此，Mint 1-CASK复合物不是AMPA和NMDA受体功能或兴奋性突触中突触可塑性所必需的。然而，在抑制性突触中，我们发现突触前成对脉冲抑制增加了约3倍，这表明Mint 1的缺失损害了γ-氨基丁酸释放的调节。我们的数据表明，薄荷糖1和2执行冗余的突触功能，这在薄荷糖1缺陷小鼠的抑制性中间神经元中变得明显，因为这些神经元选择性地表达比薄荷糖2更高水平的薄荷糖1。
Mints (also called X11-like proteins) are adaptor proteins composed of divergent N-terminal sequences that bind to synaptic proteins such as CASK (Mint 1 only) and Munc18-1 (Mints 1 and 2) and conserved C-terminal PTB- and PDZ-domains that bind to widely distributed proteins such as APP, presenilins, and Ca2+ channels (all Mints). We find that Mints 1 and 2 are similarly expressed in most neurons except for inhibitory interneurons that contain selectively high levels of Mint 1. Using knockout mice, we show that deletion of Mint 1 does not impair survival or alter the overall brain architecture, arguing against an essential developmental function of the Mint 1-CASK complex. In electrophysiological recordings in the hippocampus, we observed no changes in short- or long-term synaptic plasticity in excitatory synapses from Mint 1-deficient mice and detected no alterations in the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents. Thus the Mint 1-CASK complex is not required for AMPA- and NMDA-receptor functions or for synaptic plasticity in excitatory synapses. In inhibitory synapses, however, we uncovered an approximate to3-fold increase in presynaptic paired-pulse depression, suggesting that deletion of Mint 1 impairs the regulation of gamma-aminobutyric acid release. Our data indicate that Mints 1 and 2 perform redundant synaptic functions that become apparent in Mint 1-deficient mice in inhibitory interneurons because these neurons selectively express higher levels of Mint 1 than Mint 2.