Connexin 43 Modulates Regulated Exocytosis

连接蛋白 43 调节胞吐作用

• 批准号: 10164801
• 负责人: VLADIMIR PARPURA
• 金额: $ 33.41万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10164801
• 关键词: Address; Affect; Affinity Chromatography; Agonist; Alzheimer' s Disease; Astrocytes; Binding Sites; Biology; Bradykinin; Brain; Brain Diseases; Cell Culture Techniques; Cell membrane; Cells; Clathrin; Communication; Conflict (Psychology); Connexin 43; Connexins; Coupled; Data; Deletion Mutation; Disease; Endocytosis; Ensure; Exocytosis; Fluorescence Microscopy; Gap Junctions; Glutamate Receptor; Glutamates; Health; High Pressure Liquid Chromatography; Image; Infection; Intervention; Investigation; Ischemia; Knock-out; Laboratories; Learning; Life; Link; Literature; Location; Mediating; Memory; Microscopy; Microtubule Proteins; Microtubule Stabilization; Microtubules; Molecular; Molecular Target; Multiple Sclerosis; Mutation; Neurons; Osteoblasts; PHluorin; Pharmacology; Process; Proteins; Proteomics; Reproducibility; Resolution; Respiration; Retrieval; Role; Secretory Vesicles; Seizures; Signal Transduction; Site; Slice; Stroke; Structural Protein; Synapses; Synaptic Transmission; Techniques; Testing; Traumatic Brain Injury; Tubulin; VAMP-2; Vesicle; Work; bone; cell type; depolymerization; designer receptors exclusively activated by designer drugs; experimental study; insight; interest; novel; sleep regulation; subcellular targeting; tandem mass spectrometry; vesicular release; virtual

Abstract Astrocyte-neuron signaling, a.k.a. gliotransmission, can modulate synaptic transmission/plasticity at tripartite synapses. Among the processes regulated by gliotransmission are sleep-regulation, respiration, and learning/memory. Despite these roles of gliotransmission in such fundamental life processes, its mechanism is not understood. Elucidating this mechanism should provide insights into basic brain processes, and suggest interventions when they go awry. Two early studies of astrocyte-neuron signaling explored the hypothesis that astrocytic glutamate release acts on neuronal glutamate receptors, but they led to different conclusions regarding the mechanism. One study concluded that glutamate is not the messenger but instead suggested that gap junctions might mediate astrocyte-neuron signaling. The other study concluded that the signaling is mediated by Ca2+-dependent glutamate release from astrocytes, subsequently shown to occur by regulated exocytosis of glutamate-containing vesicles. Virtually nothing is known about the subcellular distribution/localization of astrocyte release sites. It is not clear if they are localized uniquely to the tripartite synaptic regions of astrocytes or more broadly. There is much debate about the relative roles of exocytosis vs. gap junction-mediated communication as critical for astrocyte-neuron signals. Our preliminary data point to a novel, unifying hypothesis that these two mechanisms are, in fact, mechanistically linked.

摘要 星形胶质细胞-神经元信号传导，又称神经胶质传递，可以调节突触传递/可塑性， 三联突触神经胶质传递调节的过程包括睡眠调节、呼吸和 学习/记忆尽管胶质传递在这些基本生命过程中发挥了这些作用，但其机制是 不理解。阐明这一机制将有助于深入了解基本的大脑过程，并建议 当他们出差错的时候。两项关于星形胶质细胞-神经元信号传导的早期研究探讨了以下假设： 星形胶质细胞谷氨酸释放作用于神经元谷氨酸受体，但他们得出了不同的结论 关于机制。一项研究得出结论，谷氨酸不是信使，而是暗示 缝隙连接可能介导星形胶质细胞-神经元信号传导。另一项研究得出结论，信号是 由星形胶质细胞的Ca 2+依赖性谷氨酸释放介导，随后显示通过调节 含谷氨酸囊泡的胞吐作用。事实上，我们对亚细胞 星形胶质细胞释放位点的分布/定位。目前尚不清楚它们是否只局限于三方 星形胶质细胞的突触区域或更广泛的区域。关于胞吐作用与胞吐作用的相对作用存在很多争论。 缝隙连接介导的通讯对星形胶质细胞-神经元信号至关重要。我们的初步数据显示 新的统一假设，这两种机制实际上是机械联系的。