γ-氨基丁酸（GABA）是中樞神經(jīng)系統(tǒng)中的主要抑制性神經(jīng)遞質(zhì),。從突觸上釋放出來的GABA通過作用于突觸后膜上的γ-氨基丁酸受體而對細(xì)胞的行為與生理活動(dòng)進(jìn)行調(diào)節(jié),。該受體包括GABA門控離子通道型受體（GABAAR和GABACR）和Gi/o偶聯(lián)的代謝型γ-氨基丁酸B型受體(GABABR),。
華中科技大學(xué)分子生物物理教育部重點(diǎn)實(shí)驗(yàn)室劉劍峰教授領(lǐng)銜的研究小組在神經(jīng)細(xì)胞凋亡機(jī)制研究方面取得新的進(jìn)展,，相關(guān)成果文章公布在最近的《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）上,。
研究表明多種神經(jīng)系統(tǒng)退行性疾?。ㄈ绨d癇,、精神分裂癥、亨庭頓癥等）和精神疾?。ㄈ缃箲]癥與抑郁癥等）均與在神經(jīng)系統(tǒng)廣泛表達(dá)的GABABR的功能紊亂密切相關(guān),。因此，GABABR成了多種神經(jīng)系統(tǒng)疾病和精神疾病治療的藥物靶點(diǎn),。
劉劍峰教授研究組發(fā)現(xiàn)GABABR的特異性激活后,，通過轉(zhuǎn)激活受體酪氨酸激酶, 胰島素樣生長因子1受體（IGF-1R）保護(hù)神經(jīng)元凋亡。進(jìn)一步的深入研究表明,，Gi/o蛋白,，PLC,，細(xì)胞內(nèi)鈣離子信號(hào)，和黏著斑激酶（FAK1）調(diào)節(jié)著GABABR與IGF-1R之間的相互作用（crosstalk）,，被GABABR轉(zhuǎn)激活的IGF-1R進(jìn)而誘導(dǎo)下游的Src激酶,，PI3激酶和Akt信號(hào)的激活。這些研究不僅闡明了GABABR的一種新的生理功能,，并對深入揭示了GPCR與RTK之間的協(xié)同作用在細(xì)胞間相互通信過程中起著重要的作用與生理意義,。而且提示了GABABR可以作為相關(guān)神經(jīng)系統(tǒng)退行性疾病治療的新的潛在藥物靶點(diǎn)。
參與研究的有華中科技大學(xué)分子生物物理教育部重點(diǎn)實(shí)驗(yàn)室中法聯(lián)合藥物篩選中心的博士研究生涂海軍,，許嬋娟等。(生物谷Bioon.com)
生物谷推薦原文出處：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.2343-09.2010
GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation.
Haijun Tu,1 * Chanjuan Xu,1 * Wenhua Zhang,1 Qiuyao Liu,1 Philippe Rondard,2 Jean-Philippe Pin,2 and Jianfeng Liu1
1Sino-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, and 2Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Inserm, U661 and Université Montpellier 1, 2, Montpellier F-34000, France
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, GABAB 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 GABAB 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 Gi/o-protein, PLC, cytosolic Ca2+, 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 GABAB receptor as a potential drug target for the treatment of neurodegenerative disorders.
