beta-arrestin acts as a clathrin adaptor in endocytosis of the beta(2)-adrenergic receptor
beta-arrestin acts as a clathrin adaptor in endocytosis of the beta(2)-adrenergic receptor
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DOI：
10.1038/383447a0
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发表时间：
1996-10-03
期刊：
影响因子：
64.8
通讯作者：
Benovic, JL
中科院分区：
文献类型：
--
作者：
Goodman, OB;Krupnick, JG;Benovic, JL
系统在连续刺激存在下调节其反应性的能力，通常称为脱敏，已被广泛表征为β（2）-肾上腺素能受体（β（2）AR）。β（2）AR信号通过受体磷酸化和随后的β-抑制蛋白结合而迅速减弱（1，2）。最终，受体经历内化（3，4），尽管分子机制尚不清楚，但受体磷酸化和β-抑制蛋白结合涉及该过程（5，6）。在这里，我们报告β-抑制蛋白和抑制蛋白-3，但不是视觉抑制蛋白，促进β（2）AR内化，并以高亲和力直接和化学计量结合到网格蛋白，包被的小凹的主要结构蛋白。此外，β-抑制蛋白/抑制蛋白嵌合体，无论是在β（2）AR或网格蛋白结合缺陷显示降低的能力，以促进β（2）AR内吞。完整细胞的免疫荧光显微镜显示激动剂依赖性的β 2 AR和β-arrestin与网格蛋白的共定位。这些结果表明β-arrestin在受体介导的内吞途径中起衔接子的作用，并提出了调节G蛋白偶联受体运输的一般机制。
THE ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the beta(2)-adrenergic receptor (beta(2)AR). beta(2)AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin(1,2). Ultimately the receptor undergoes internalization(3,4), and although the molecular mechanism is unclear, receptor phosphorylation and beta-arrestin binding have been implicated in this process(5,6). Here we report that beta-arrestin and arrestin-3, but not visual arrestin, promote beta(2)AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits, Moreover, beta-arrestin/arrestin chimaeras that are defective in either beta(2)AR or clathrin binding show a reduced ability to promote beta(2)AR endocytosis. Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the beta(2)AR and beta-arrestin with clathrin, These results show that beta-arrestin functions as an adaptor in the receptor-mediated endocytosis pathway, and suggest a general mechanism for regulating the trafficking of G-protein-coupled receptors.