Hennou Sonia, Kato Akihiko, Schneider Edith M, Lundstrom Kenneth, Gähwiler Beat H, Inokuchi Kaoru, Gerber Urs, Ehrengruber Markus U
Brain Research Institute, University of Zurich, Zurich, Switzerland.
Eur J Neurosci. 2003 Aug;18(4):811-9. doi: 10.1046/j.1460-9568.2003.02812.x.
Homer/Vesl proteins are involved in regulating metabotropic glutamate receptors, synaptogenesis, dendritic spine development and axonal pathfinding. We investigated the potential modulation of glutamatergic synaptic transmission by the immediate early gene product Homer-1a/Vesl-1S and by the constitutively expressed long-form Homer-1c/Vesl-1L in CA1 pyramidal cells from cultured rat hippocampal slices. Semliki Forest virus vector-mediated overexpression of Homer-1a enhanced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, but did not detectably affect N-methyl-d-aspartate (NMDA) receptor function and presynaptic glutamate release. Overexpression of Homer-1c, by contrast, did not alter synaptic transmission. To corroborate our electrophysiological results obtained in slice cultures, we performed quantitative immunocytochemistry in cultures of dissociated hippocampal neurons. Homer-1a also increased synaptic clustering of AMPA but not NMDA receptors, whereas Homer-1c had no detectable effect. Our results show that Homer-1a potentiates synaptic AMPA receptor function, supporting a critical role for Homer-1a in hippocampal synaptic plasticity.
荷马/维斯尔蛋白参与调节代谢型谷氨酸受体、突触形成、树突棘发育和轴突导向。我们研究了即刻早期基因产物荷马-1a/维斯尔-1S以及组成型表达的长型荷马-1c/维斯尔-1L对培养的大鼠海马切片CA1锥体细胞中谷氨酸能突触传递的潜在调节作用。辛德毕斯病毒载体介导的荷马-1a过表达增强了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体功能，但未检测到对N-甲基-D-天冬氨酸（NMDA）受体功能和突触前谷氨酸释放的影响。相比之下，荷马-1c的过表达并未改变突触传递。为了证实我们在切片培养中获得的电生理结果，我们在解离的海马神经元培养物中进行了定量免疫细胞化学实验。荷马-1a也增加了AMPA而非NMDA受体的突触聚集，而荷马-1c则未检测到明显影响。我们的结果表明，荷马-1a增强了突触AMPA受体功能，支持了荷马-1a在海马突触可塑性中起关键作用。
