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首页> 外文期刊>The Journal of biological chemistry >Sodium-Hydrogen Exchanger Regulatory Factor 1 (NHERF-1) Transduces Signals That Mediate Dopamine Inhibition of Sodium-Phosphate Co-transport in Mouse Kidney
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Sodium-Hydrogen Exchanger Regulatory Factor 1 (NHERF-1) Transduces Signals That Mediate Dopamine Inhibition of Sodium-Phosphate Co-transport in Mouse Kidney

机译：氢化氢交换剂调节因子1（NERF-1）转换介导多巴胺抑制磷酸钠共传输的信号的信号

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Dopamine inhibited phosphate transport in isolated renal brush border membrane vesicles and in cultured renal proximal tubule cells from wild-type but not from NHERF-1 null mice. Co-immunoprecipitation experiments established that NHERF-1 associated with D1-like receptors. In wild-type mice, dopamine stimulated cAMP accumulation and protein kinase C (PKC) activity in renal proximal tubule cells, an effect that was abolished by SCH-23390, a D1-like receptor antagonist. In NHERF-1 null kidney tissue; however, dopamine failed to stimulate either cAMP accumulation or PKC activity. Infection of proximal tubule cells from NHERF-1 null mice with adenovirus-green fluorescent protein-NHERF-1 restored the ability of dopamine to stimulate cAMP and PKC. Finally, in 32P-labeled wild-type proximal tubule cells and in opossum kidney cells, dopamine increased NHERF-1 phosphorylation at serine 77 of the PDZ I domain of NHERF-1, a site previously shown to attenuate binding of cellular targets including the Npt2a (sodium-dependent phosphate transporter 2a). Together, these studies establish that NHERF-1 plays a key role in dopamine signaling and is also a downstream target of D1-like receptors in the mouse kidney. These studies suggest a novel role for the PDZ adapter protein NHERF-1 in coordinating dopamine signals that inhibit renal phosphate transport.
机译：多巴胺在野生型中抑制分离的肾刷界膜囊泡中的磷酸盐输送，但培养肾近端小管细胞，但不是来自NHERF-1零小鼠。共同免疫沉淀实验确定了与D1样受体相关的NHERF-1。在野生型小鼠中，多巴胺刺激的CAMP积累和蛋白激酶C（PKC）活性在肾近端小管细胞中，SCH-23390废除的效果是D1样受体拮抗剂。在Nurf-1纯肾组织中;然而，多巴胺未能刺激营地积累或PKC活性。用腺病毒 - 绿色荧光蛋白-NERF-1感染来自NHERF-1零小鼠的近端小鼠细胞恢复了多巴胺刺激营和PKC的能力。最后，在32P标记的野生型近端小管细胞和在扑乳肾细胞中，多巴胺在NHERF-1的PDZ I结构域的丝塞77中增加了NHERF-1磷酸化，前面示出了衰减包括NPT2a的细胞靶标的结合（依赖磷酸钠转运蛋白2a）。这些研究共同建立了NHERF-1在多巴胺信号传导中起关键作用，并且也是小鼠肾脏中D1样受体的下游靶。这些研究表明PDZ适配器蛋白NHERF-1在协调抑制肾磷酸盐转运的多巴胺信号中的一种新作用。

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