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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >The scaffold protein NHERF2 determines the coupling of P2Y1 nucleotide and mGluR5 glutamate receptor to different ion channels in neurons.
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The scaffold protein NHERF2 determines the coupling of P2Y1 nucleotide and mGluR5 glutamate receptor to different ion channels in neurons.

机译:支架蛋白NHERF2确定P2Y1核苷酸和mGluR5谷氨酸受体与神经元中不同离子通道的偶联。

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摘要

Expressed metabotropic group 1 glutamate mGluR5 receptors and nucleotide P2Y1 receptors (P2Y1Rs) show promiscuous ion channel coupling in sympathetic neurons: their stimulation inhibits M-type [Kv7, K(M)] potassium currents and N-type (Ca(V)2.2) calcium currents (Kammermeier and Ikeda, 1999; Brown et al., 2000). These effects are mediated by G(q) and G(i/o) G-proteins, respectively. Via their C-terminal tetrapeptide, these receptors also bind to the PDZ domain of the scaffold protein NHERF2, which enhances their coupling to G(q)-mediated Ca(2+) signaling (Fam et al., 2005; Paquet et al., 2006b). We investigated whether NHERF2 could modulate coupling to neuronal ion channels. We find that coexpression of NHERF2 in sympathetic neurons (by intranuclear cDNA injections) does not affect the extent of M-type potassium current inhibition produced by either receptor but strongly reduced Ca(V)2.2 inhibition by both P2Y1R and mGluR5 activation. NHERF2 expression had no significant effect on Ca(V)2.2 inhibition by norepinephrine (via alpha(2)-adrenoceptors, which do not bind NHERF2), nor on Ca(V)2.2 inhibition produced by an expressed P2Y1R lacking the NHERF2-binding DTSL motif. Thus, NHERF2 selectively restricts downstream coupling of mGluR5 and P2Y1Rs in neurons to G(q)-mediated responses such as M-current inhibition. Differential distribution of NHERF2 in neurons may therefore determine coupling of mGluR5 receptors and P2Y1 receptors to calcium channels.
机译:表达的代谢型1组谷氨酸mGluR5受体和核苷酸P2Y1受体(P2Y1Rs)在交感神经元中显示混杂的离子通道偶联:它们的刺激抑制M型[Kv7,K(M)]钾电流和N型(Ca(V)2.2)钙流(Kammermeier和Ikeda,1999; Brown等,2000)。这些作用分别由G(q)和G(i / o)G蛋白介导。通过它们的C末端四肽,这些受体还与支架蛋白NHERF2的PDZ域结合,从而增强了它们与G(q)介导的Ca(2+)信号传导的偶联(Fam等人,2005; Paquet等人。 ,2006b)。我们调查了NHERF2是否可以调节耦合到神经元离子通道。我们发现,交感神经元中NHERF2的共表达(通过核内cDNA注射)不会影响任一受体产生的M型钾电流抑制的程度,但会通过P2Y1R和mGluR5激活强烈降低Ca(V)2.2抑制。 NHERF2表达对去甲肾上腺素对Ca(V)2.2的抑制作用没有显着影响(通过不与NHERF2结合的alpha(2)-肾上腺素受体),对表达缺乏NHERF2结合的DTSL的P2Y1R产生的Ca(V)2.2抑制作用也没有主题。因此,NHERF2选择性地限制神经元中的mGluR5和P2Y1R下游耦合到G(q)介导的反应,例如M电流抑制。因此,神经元中NHERF2的差异分布可能决定mGluR5受体和P2Y1受体与钙通道的偶联。

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