González Marco I
Department of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Neurochem Int. 2014 Jun;72:14-21. doi: 10.1016/j.neuint.2014.04.006. Epub 2014 Apr 18.
Fast synaptic inhibition in the adult brain is largely mediated by GABAA receptors (GABAAR). GABAAR are anchored to synaptic sites by gephyrin, a scaffolding protein that appears to be assembled as a hexagonal lattice beneath the plasma membrane. Brain derived neurotrophic factor (BDNF) alters the clustering and synaptic distribution of GABAAR but mechanisms behind this regulation are just starting to emerge. The current study was aimed to examine if BDNF alters the protein levels and/or clustering of gephyrin and to investigate whether the modulation of gephyrin is accompanied by changes in the distribution and/or clustering of GABAAR. Exogenous application of BDNF to immature neuronal cultures from rat hippocampus increased the protein levels and clustering of gephyrin. BDNF also augmented the association of gephyrin with GABAAR and promoted the formation of GABAAR clusters. Together, these observations indicate that BDNF might regulate the assembly of GABAergic synapses by promoting the association of GABAAR with gephyrin.
在成人大脑中，快速突触抑制主要由γ-氨基丁酸A型受体（GABAAR）介导。GABAAR通过gephyrin锚定在突触部位，gephyrin是一种支架蛋白，似乎组装成质膜下方的六边形晶格。脑源性神经营养因子（BDNF）会改变GABAAR的聚集和突触分布，但这种调节背后的机制才刚刚开始显现。当前的研究旨在检验BDNF是否会改变gephyrin的蛋白质水平和/或聚集，并研究gephyrin的调节是否伴随着GABAAR分布和/或聚集的变化。将BDNF外源应用于大鼠海马的未成熟神经元培养物中，可增加gephyrin的蛋白质水平和聚集。BDNF还增强了gephyrin与GABAAR的结合，并促进了GABAAR簇的形成。总之，这些观察结果表明，BDNF可能通过促进GABAAR与gephyrin的结合来调节GABA能突触的组装。
