GABA A RECEPTOR STRUCTURE AND FUNCTION

GABA A 受体结构和功能

• 批准号: 6262755
• 负责人: RICHARD W OLSEN
• 金额: $ 25.27万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6262755
• 关键词: GABA receptor; PC12 cells; cytoskeleton; enzyme activity; gamma aminobutyrate; immunofluorescence technique; intermolecular interaction; neuropharmacology; phosphoproteins; phosphorylation; protein biosynthesis; protein isoforms; protein kinase C; protein structure function; recombinant proteins; synthetic peptide; voltage /patch clamp; western blottings

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.

GABAA受体（GABAR）介导了中枢神经系统（CNS）中大部分快速抑制性突触传播，因此对于正常和疾病CNS功能至关重要。在药理学和生物学特性中，有一个类似但独特的Gabar亚型的家族。另外，Gabar位于神经元细胞膜的不同部分，突触培养物以及非突触膜中。刚刚开始研究突触受体的贩运，靶向，聚类和营业额。特别是，与GABAR的细胞内结构域相互作用的细胞蛋白可以在突触处的突触处锚定和聚类受体，以及在可塑性事件中建立和重建突触及其受体。我们将研究与Gabar相互作用的几种细胞蛋白的功能，我们使用酵母双杂交系统鉴定出来。 GABARAP（GABA受体相关蛋白）将GABAR GAMMA2亚基与突触时的微管和簇Gabar联系起来。 RACK1（激活C-激酶的受体）将蛋白激酶C-beta与Gabar Alpha1亚基联系起来，可能是用于通过PKC通过蛋白质磷酸化来调节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仔细研究这些重要的脑神经递质受体的动态和重要的细胞生物学。