Substance P-induced trafficking of β-arrestins -: The role of β-arrestins in endocytosis of the neutrokinin-1 receptor
Substance P-induced trafficking of β-arrestins -: The role of β-arrestins in endocytosis of the neutrokinin-1 receptor
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DOI：
10.1074/jbc.274.23.16257
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发表时间：
1999-06-04
影响因子：
4.8
通讯作者：
Bunnett, NW
中科院分区：
文献类型：
--
作者：
McConalogue, K;Déry, O;Bunnett, NW
激动剂诱导的 G 蛋白偶联受体 (GPCR) 和 β-抑制蛋白的重新分布决定了随后的细胞对激动剂的反应，并且对于信号转导非常重要。我们使用绿色荧光蛋白实时检测 KNRK 细胞中 P 物质 (SP) 诱导的 β-arrestin1 和神经激肽-1 受体 (NK1R) 的运输。绿色荧光蛋白不会改变 NK1R 或 beta-arrestin1 的功能或定位，SP 诱导 (a) 引人注目且快速（60 分钟）； (d) 质膜上的 NK1R 和细胞质中的 β-arrestin1 逐渐恢复稳态分布（4-6 小时），SP 刺激了免疫反应性 β-arrestin1 和 β-arrestin2 的类似重新分布。相反，SP不影响Gα(q/11)分布，其保留在质膜上。显性失活β-抑制蛋白(319-418)的表达抑制SP诱导的NK1R内吞作用，因此，SP诱导β-抑制蛋白快速易位至质膜，在那里它们参与NK1R内吞作用。 β-抑制蛋白在内体中与 NK1R 共定位，直到 NK1R 循环并且 β-抑制蛋白返回细胞质。
Agonist-induced redistribution of G-protein-coupled receptors (GPCRs) and beta-arrestins determines the subsequent cellular responsiveness to agonists and is important for signal transduction. We examined substance P (SP)-induced trafficking of beta-arrestin1 and the neurokinin-1 receptor (NK1R) in KNRK cells in real time using green fluorescent protein. Green fluorescent protein did not alter function or localization of the NK1R or beta-arrestin1, SP induced (a) striking and rapid (60 min); (d) gradual resumption of the steady state distribution of the NK1R at the plasma membrane and beta-arrestin1 in the cytosol (4-6 h), SP stimulated a similar redistribution of immunoreactive beta-arrestin1 and beta-arrestin2. In contrast, SP did not affect G alpha(q/11) distribution, which remained at the plasma membrane. Expression of the dominant negative beta-arrestin(319-418) inhibited SP-induced endocytosis of the NK1R, Thus, SP induces rapid translocation of beta-arrestins to the plasma membrane, where they participate in NK1R endocytosis. beta-Arrestins colocalize with the NK1R in endosomes until the NK1R recycles and beta-arrestins return to the cytosol.