突触前蛋白协调动态相互作用的复杂相互作用,以调节递质填充囊泡的定量胞吐作用,它们的失调可能会导致神经和神经精神功能障碍。小鼠在皮质中囊泡谷氨酸转运体2(Vglut2;akaSlc17a6)的表达存在时空限制,出生后第三周的杏仁核和海马下丘显示出强烈的抗焦虑表型和精神分裂症的某些行为相关性。为了进一步了解Vglut2的这种靶向缺失的分子后果,我们进行了无偏倚的微阵列分析,比较了这些条件性Vglut2敲除小鼠(Vglut2f/f;CamKIIcKO)与对照同窝动物中的基因表达水平。Unc13C(Munc13-3)的表达,Unc/Munc家族的成员,以前被证明对谷氨酸能传递很重要,被确定为显著下调。随后通过定量RT-PCR分析显示Munc13-1下调了50%,该基因编码Unc/Munc亚型,被描述为海马中大多数谷氨酸能突触的必需成分。还发现编码突触前机制的其他成分的基因受到调控,包括Rab3A,RIM1α,以及Syntaxin1和Synaptobrevin。在杏仁核和皮质的脾后组中进一步发现了这些基因的表达水平的改变,有条件地靶向Vglut2的其他区域。这些发现表明,Vglut2的表达水平对于维持成年小鼠大脑突触前机制中的基因表达可能很重要。突触68:624-633,2014。©2014Wiley期刊,Inc.
Presynaptic proteins orchestrate an intricate interplay of dynamic interactions in order to regulate quantal exocytosis of transmitter-filled vesicles, and their dysregulation might cause neurological and neuropsychiatric dysfunction. Mice carrying a spatiotemporal restriction in the expression of the Vesicular glutamate transporter 2 (Vglut2; aka
Slc17a6) in the cortex, amygdala and hippocampal subiculum from the third postnatal week show a strong anxiolytic phenotype and certain behavioral correlates of schizophrenia. To further understand the molecular consequences of this targeted deletion of Vglut2, we performed an unbiased microarray analysis comparing gene expression levels in the subiculum of these conditional Vglut2 knockout mice (Vglut2f/f;CamKII cKO) to those in control littermates. Expression of Unc13C (Munc13-3), a member of the Unc/Munc family, previously shown to be important for glutamatergic transmission, was identified to be significantly down-regulated. Subsequent analysis by quantitative RT-PCR revealed a 50% down-regulation of Munc 13-1, the gene encoding the Unc/Munc subtype described as an essential component in the majority of glutamtergic synapses in the hippocampus. Genes encoding additional components of the presynaptic machinery were also found regulated, including Rab3A, RIM1α, as well as Syntaxin1 and Synaptobrevin. Altered expression levels of these genes were further found in the amygdala and in the retrosplenial group of the cortex, additional regions in which Vglut2 was conditionally targeted. These findings suggest that expression levels of Vglut2 might be important for the maintenance of gene expression in the presynaptic machinery in the adult mouse brain. Synapse 68:624-633, 2014. © 2014 Wiley Periodicals, Inc.