GABA A RECEPTOR STRUCTURE AND FUNCTION

GABAA受体（GABAR）介导中枢神经系统（CNS）的大部分快速抑制性突触传递，因此对正常和疾病中枢神经系统功能至关重要。有一个相似但不同的GABAR亚型家族，其药理和生物学特性各不相同。此外，GABAR位于神经元细胞膜的不同部位、突触培养物和非突触膜中。突触受体的转运、靶向、聚类和转换的研究才刚刚开始。特别是，与GABAR胞内结构域相互作用的细胞蛋白可能在突触中锚定和聚集突触中的受体，以及在可塑性事件中建立和重建突触及其受体。我们将研究几种与GABAR相互作用的细胞蛋白的功能，我们使用酵母双杂交系统确定了这些蛋白。GABARAP （GABA受体相关蛋白）将GABAR γ ma2亚基连接到微管并在突触聚集GABAR。RACK1（活化c激酶受体）将蛋白激酶c - β与GABAR α 1亚基连接，可能通过PKC蛋白磷酸化调节GABAR功能的某些方面。对这些和相关蛋白质的研究将使我们能够近距离观察这些重要的脑神经递质受体的动态和重要的细胞生物学。

GABAA receptors (GABAR) mediate the bulk of rapid inhibitory synaptic transmission in the central nervous system (CNS), and are thus critical to normal and disease CNS function. There are a family of similar but distinct GABAR subtypes which vary in pharmacological and biological properties. In addition GABAR are located in different parts of the neuronal cell membrane and in synaptic cultures as well as non- synaptic membrane. The trafficking, targeting, clustering, and turnover of synaptic receptors in just beginning to be studied. In particular, cellular proteins that interact with the intracellular domains of GABAR may serve to anchor and cluster receptors at synapses at synapses, as well as to establish and reconstruct synapses and their receptors during plasticity events. We will study the function of several cellular proteins that interact with GABAR that we identified using the yeast two-hybrid system. GABARAP (GABA Receptor Associated Protein) links GABAR gamma2 subunit to microtubules and clusters GABAR at synapses. RACK1 (receptor for activated C-kinase), links protein kinase C-beta to GABAR alpha1 subunit, probably for regulating some aspect of GABAR function by protein phosphorylation with PKC. Studies on these and related proteins will allow us to take a close look a dynamic and important cellular biology of these important brain neurotransmitter receptors.