GABA_B受体与跨膜受体交叉对话研究新进展

Functional Crosstalk between GABA_B Receptors and Other Trans-Membrane Receptors

γ-氨基丁酸(γ-aminobutyric acid,GABA)B型受体是中枢神经系统中抑制性神经递质GABA的代谢型受体,属于G蛋白偶联受体(G-protein-coupled receptor,GPCR)C家族成员,激活后介导缓慢持久的神经抑制效应,在突触可塑性方面起重要调节作用,是很多神经类疾病的重要药物靶点。GABAB受体必须由GABAB1(GB1)和GABAB2(GB2)两个亚基形成异源二聚体才能发挥功能。近期研究发现,GABAB受体除了单独激活下游信号通路外,还可以和其它跨膜受体,包括离子型受体、其它GPCR以及受体酪氨酸激酶等通过直接或间接相互作用发生交叉对话(crosstalk),并在不同水平上动态调节GABAB受体介导的下游信号,从而影响新的细胞生理功能。膜受体之间信号通路上的crosstalk将为相关疾病提供新的治疗策略。

GABAB receptors are members of Class C GPCRs which bind the GABA, the main inhibitory neurotransmitter in the central nervous system. Activation of GABAB receptors mediate slow inhibitory neurotransmission and play important roles in regulating synaptic plasticity. It is a promising drug target for a variety of neurological disorders. Previous studies showed that heterodimerization of GB1 and GB2 is required for the formation of functional receptors. However, in addition to activating downstream signaling pathways alone, recent studies found that GABAB receptor can induce crosstalk with other tranmembrane receptors by direct or indirect interactions, leading to synergistic or new signaling responses which play important roles in physiological functions. Understanding the molecular mechanisms of crosstalk in transmembrane receptors will provide new therapeutic strategies for diseases.