An intracellular motif of P2X3 receptors is required for functional cross‐talk with GABAA receptors in nociceptive DRG neurons
An intracellular motif of P2X3 receptors is required for functional cross‐talk with GABAA receptors in nociceptive DRG neurons
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DOI：
10.1111/j.1471-4159.2007.04640.x
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发表时间：
2007-08
影响因子：
4.7
通讯作者：
Estelle Toulmé;D. Blais;C. Léger;M. Landry;M. Garret;P. Séguéla;E. Boué-Grabot
中科院分区：
文献类型：
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作者：
Estelle Toulmé;D. Blais;C. Léger;M. Landry;M. Garret;P. Séguéla;E. Boué-Grabot
结构不相关的P2X ATP受体和“cys - loop”受体-通道超家族成员之间的功能串扰代表了最近发现的快速调节信息处理的机制。然而，这两类嗜离子受体之间的抑制性交叉对话的程度和机制仍然知之甚少。离子偶联和分子偶联被认为可以解释P2X亚型和GABAA受体之间的交叉抑制，这表明P2X亚基依赖机制。我们在这里表明，神经元P2X3或P2X2+3与GABAA受体之间的交叉抑制不依赖于氯离子和钙离子。我们在P2X3亚基中发现了一个胞内QST386-388基序，这是与GABAA受体功能偶联所必需的。此外，在培养的大鼠背根神经节（DRG）神经元中，天然P2X3和GABA受体之间的交叉抑制可以通过输注含有QST基序的肽以及病毒表达GABA β3亚基的主要细胞内环来消除。我们提供的证据表明，P2X3和GABAA受体共定位于伤害性DRG神经元的体细胞和中枢过程中，这表明细胞内特定的P2X3 - GABAA亚基相互作用是突触前串扰的基础，可能有助于调节脊髓中的感觉突触传递。
Functional cross‐talk between structurally unrelated P2X ATP receptors and members of the ‘cys‐loop’ receptor‐channel superfamily represents a recently‐discovered mechanism for rapid modulation of information processing. The extent and the mechanism of the inhibitory cross‐talks between these two classes of ionotropic receptors remain poorly understood, however. Both ionic and molecular coupling were proposed to explain cross‐inhibition between P2X subtypes and GABAA receptors, suggesting a P2X subunit‐dependent mechanism. We show here that cross‐inhibition between neuronal P2X3 or P2X2+3 and GABAA receptors does not depend on chloride and calcium ions. We identified an intracellular QST386–388 motif in P2X3 subunits which is required for the functional coupling with GABAA receptors. Moreover the cross‐inhibition between native P2X3 and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is abolished by infusion of a peptide containing the QST motif as well as by viral expression of the main intracellular loop of GABAAβ3 subunits. We provide evidence that P2X3 and GABAA receptors are colocalized in the soma and central processes of nociceptive DRG neurons, suggesting that specific intracellular P2X3‐GABAA subunit interactions underlie a pre‐synaptic cross‐talk that might contribute to the regulation of sensory synaptic transmission in the spinal cord.