Klugmann Matthias, Szumlinski Karen K
Department of Physiological Chemistry, University of Mainz, Mainz, Germany.
Behav Pharmacol. 2008 Sep;19(5-6):485-500. doi: 10.1097/FBP.0b013e32830c369f.
Over a decade of in-vitro data support a critical role for members of the Homer family of postsynaptic scaffolding proteins in regulating the functional architecture of glutamate synapses. Earlier studies of Homer knockout mice indicated a necessary role for Homer gene products in normal mesocorticolimbic glutamate transmission and behaviours associated therewith. The advent of adeno-associated viral vectors carrying cDNA for, or short hairpin RNA against, specific Homer isoforms enabled the site-directed targeting of Homers to neurons in the brain. This approach has allowed our groups to address developmental issues associated with conventional knockout mice, to confirm active roles for distinct Homer isoforms in regulating glutamate transmission in vivo, as well as in mediating a variety of behavioural processes. This review summarizes the existing data derived from our studies using adeno-associated viral vector-mediated neuronal targeting of Homer in rodents, implicating this family of proteins in drug and alcohol addiction, learning/memory and emotional processing.
十多年的体外实验数据支持了突触后支架蛋白荷马家族成员在调节谷氨酸突触功能结构中发挥关键作用。早期对荷马基因敲除小鼠的研究表明，荷马基因产物在正常的中脑皮质边缘谷氨酸传递及与之相关的行为中起必要作用。携带特定荷马异构体的互补脱氧核糖核酸（cDNA）或短发夹RNA的腺相关病毒载体的出现，使得能够将荷马蛋白定点靶向到大脑中的神经元。这种方法使我们的研究团队能够解决与传统基因敲除小鼠相关的发育问题，证实不同的荷马异构体在体内调节谷氨酸传递以及介导多种行为过程中发挥的积极作用。本综述总结了我们利用腺相关病毒载体介导的在啮齿动物中对荷马蛋白进行神经元靶向研究得出的现有数据，表明该蛋白家族与药物和酒精成瘾、学习/记忆及情绪处理有关。
