Desensitization of the neurokinin-1 receptor (NK1-R) in neurons:: Effects of substance P on the distribution of NK1-R, Gαq/11 G-protein receptor kinase-2/3, and β-arrestin-1/2
Desensitization of the neurokinin-1 receptor (NK1-R) in neurons:: Effects of substance P on the distribution of NK1-R, Gαq/11 G-protein receptor kinase-2/3, and β-arrestin-1/2
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DOI：
10.1091/mbc.9.8.2305
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发表时间：
1998-08-01
影响因子：
3.3
通讯作者：
Bunnett, NW
中科院分区：
文献类型：
--
作者：
McConalogue, K;Corvera, CU;Bunnett, NW
在重建系统和转染细胞中的观察表明，G蛋白受体激酶（GRK）和β-抑制蛋白介导G蛋白偶联受体的脱敏和内吞作用。对神经元中的受体调节知之甚少。因此，我们研究了神经递质P物质（SP）对神经激肽-1受体（NK 1-R）脱敏的影响，以及对培养的肌间神经元中NK 1-R、G（α q/11）、GRK-2和-3以及β-arrestin-1和-2的亚细胞分布的影响。在神经元亚群中，NK 1-R与免疫反应性G（α q/11）、GRK-2和-3以及β-arrestin-1和-2共表达。SP引起NK_（1-R）介导的[Ca ~（2+）]（i）迅速升高，但这种升高是短暂的，对反复刺激不敏感;和3）β-抑制蛋白-1和-2从胞质溶胶到质膜的快速和瞬时再分布，随后，β-arrestin-1和β-arrestin-2显著重新分布到含有NK 1-R和SP的内体中。（α q/11）保留在质膜上，GRK-2和-3保留在位于中心和表面的囊泡中。因此，SP诱导神经元中NK 1-R的脱敏和内吞作用，这可能由GRK-2和-3以及β-arrestin-1和-2介导。这种调节将决定表达NK 1-R的神经元是否参与功能重要的反射。
Observations in reconstituted systems and transfected cells indicate that G-protein receptor kinases (GRKs) and beta-arrestins mediate desensitization and endocytosis of G-protein-coupled receptors. Little is known about receptor regulation in neurons. Therefore, we examined the effects of the neurotransmitter substance P (SP) on desensitization of the neurokinin-1 receptor (NK1-R) and on the subcellular distribution of NK1-R, G(alpha q/11), GRK-2 and -3, and beta-arrestin-1 and -2 in cultured myenteric neurons. NK1-R was coexpressed with immunoreactive G(alpha q/11), GRK-2 and -3, and beta-arrestin-1 and -2 in a subpopulation of neurons. SP caused 1) rapid NK1-R-mediated increase in [Ca2+](i), which was transient and desensitized to repeated stimulation; 2) internalization of the NK1-R into early endosomes containing SP; and 3) rapid and transient redistribution of beta-arrestin-1 and -2 from the cytosol to the plasma membrane, followed by a striking redistribution of beta-arrestin-1 and -2 to endosomes containing the NK1-R and SP. In SP-treated neurons G(alpha q/11) remained at the plasma membrane, and GRK-2 and -3 remained in centrally located and superficial vesicles. Thus, SP induces desensitization and endocytosis of the NK1-R in neurons that may be mediated by GRK-2 and -3 and beta-arrestin-1 and -2. This regulation will determine whether NK1-R-expressing neurons participate in functionally important reflexes.