Mechanisms for synaptic localization of ionotropic GABA receptors in the brain

大脑中离子型 GABA 受体突触定位的机制

• 批准号: 10056230
• 负责人: Susumu Tomita
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-15 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056230
• 关键词: Brain; Brain Diseases; Cell Adhesion Molecules; Cellular biology; Complex; Disease; Epilepsy; Functional disorder; GABA Receptor; Glutamate Receptor; Glutamates; Goals; Health; Heterogeneity; Human; Impairment; Inhibitory Synapse; Knockout Mice; Knowledge; Laboratories; Link; Mediating; Mental disorders; Molecular; Neurobiology; Neurons; Neurotransmitter Receptor; Play; Positioning Attribute; Presynaptic Terminals; Property; Protein Family; Regulation; Research; Role; Schizophrenia; Site; Synapses; Synaptic Receptors; Synaptic Transmission; Work; autism spectrum disorder; collybistin; gamma-Aminobutyric Acid; gephyrin; in vivo; kainate; molecular drug target; nervous system disorder; neuroligin 2; neurotransmitter release; new therapeutic target; novel; receptor; receptor function; transmission process

The activation of neurotransmitter receptors at synapses mediate synaptic transmission upon being bound by neurotransmitters released from presynaptic terminals. The predominant inhibitory transmitter in the brain is gamma-aminobutyric acid (GABA), and ionotropic GABAA receptors localize at inhibitory synapses to mediate fast inhibitory transmission. Dysregulation of GABA receptors causes various mental and neurological disorders including autism spectrum disorder, schizophrenia, epilepsy, and other disorders. However, precise mechanisms for synaptic localization of GABAA receptors remain unclear. We have recently identified novel GARLH family proteins as a critical regulator of synaptic GABAARs. In this proposal, we aim to reveal in vivo roles of GARLHs in regulating GABAAR activity in the brain, principle rules of GARLH-GABAAR interactions, and molecular relationships of constituents of inhibitory synapses. Successful completion of this proposed work will reveal fundamental molecular mechanisms for determining synaptic localization and transmission of GABAA receptors in the brain. Elucidating the molecular rules governing inhibitory transmission will enable us to identify putative molecular targets for drugs that may alleviate impair neurological and mental disorders.

突触神经递质受体的激活介导突触传递