GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation
txq01001 添加于 2010-4-15 08:51
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作 者
Tu H, Xu C, Zhang W, Liu Q, Rondard P, Pin J-P, Liu J 摘 要
The G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) play key roles in cell-cell communication. Several studies revealed important synergisms between these two types of receptors, with some of the actions of either receptor being mediated through transactivation of the other. Among the large GPCR family, GABA(B) receptor is activated by the neurotransmitter GABA, and is expressed in most neurons where it mediates slow and prolonged inhibition of synaptic transmission. Here we show that this receptor is involved in the regulation of life and death decisions of cerebellar granule neurons (CGNs). We show that specific activation of GABA(B) receptor can protect neurons from apoptosis through a mechanism that involves transactivation of the IGF-1 receptor (IGF-1R). Further work demonstrated that this cross talk was dependent on G(i/o)-protein, PLC, cytosolic Ca(2+), and FAK1 but independent of PKC, while IGF-1R-induced signaling involved Src kinase, PI3 kinase, and Akt activation. These results reveal a new function for this important GPCR and further highlight the importance of functional cross-talk networks between GPCRs and RTKs. Our results reveal GABA(B) receptor as a potential drug target for the treatment of neurodegenerative disorders.-
详细资料
- 关键词: Animals; Animals, Newborn; Apoptosis/drug effects/*physiology; Baclofen/pharmacology; Bicuculline/pharmacology; Calcium/metabolism; Caspase 3/metabolism; Cells, Cultured; Cerebellum/cytology; Chromones/pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; GABA Agonists/pharmacology; GABA Antagonists/pharmacology; In Situ Nick-End Labeling/methods; Mice; Mice, Inbred Strains; Models, Biological; Morpholines/pharmacology; Neurons/drug effects/*physiology; Oncogene Protein
- 文献种类:期刊
- 期刊名称: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
- 期刊缩写: J Neurosci
- 期卷页: 2010年 第30卷 第2期 749-759页
- 地址: Sino-France Laboratory for Drug Screening, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, Hubei, China
- ISBN: 0270-6474
- 备注:PMID:20071540
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