Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules
Interacting molecule of AT1 receptor, ATRAP, is colocalized with AT1 receptor in the mouse renal tubules
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DOI：
10.1038/sj.ki.5000130
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发表时间：
2006-02-01
影响因子：
19.6
通讯作者：
Umemura, S
中科院分区：
文献类型：
--
作者：
Tsurumi, Y;Tamura, K;Umemura, S
肾脏中的肾素-血管紧张素系统通过激活血管、肾小球和肾小管血管紧张素II 1型（AT 1）受体介导的信号传导，在肾血流动力学和钠处理的调节中发挥关键作用。我们以前克隆了一种分子，它特异性地结合到AT 1受体上，并在体外调节AT 1受体信号，我们将其命名为ATRAP（AT 1受体相关蛋白）。本研究的目的是分析ATRAP的肾脏分布，并检查ATRAP是否与AT 1受体在小鼠肾脏中共表达。我们采用原位杂交、免疫印迹和免疫组织化学方法研究了ATRAP mRNA和蛋白在小鼠肾脏中的表达。Western blot分析结果显示ATRAP蛋白在肾脏中大量表达。应用原位杂交和免疫组织化学方法，我们发现ATRAP mRNA和蛋白质广泛分布于从Bowman囊到内髓集合管的肾小管沿着。在肾小球、血管和间质细胞中也检测到ATRAP mRNA。在所有肾小管细胞中，ATRAP蛋白与AT 1受体共定位。最后，我们发现，饮食中的盐耗竭显着降低肾脏ATRAP和AT 1受体的表达。这些发现表明ATRAP在表达AT 1受体的肾单位节段中大量且广泛地分布。此外，这是第一个报告，证明了大量的ATRAP和AT 1受体在体内共定位。
The renin-angiotensin system in the kidney plays a critical role in the regulation of renal hemodynamics and sodium handling through the activation of vascular, glomerular and tubular angiotensin II type 1 (AT1) receptor-mediated signaling. We previously cloned a molecule that specifically bound to the AT1 receptor and modulated AT1 receptor signaling in vitro, which we named ATRAP ( for AT1 receptor-associated protein). The purpose of this study is to analyze the renal distribution of ATRAP and to examine whether ATRAP is co-expressed with the AT1 receptor in the mouse kidney. We performed in situ hybridization, Western blot analysis, and immunohistochemistry to investigate the expression of ATRAP mRNA and protein in the mouse kidney. The results of Western blot analysis revealed the ATRAP protein to be abundantly expressed in the kidney. Employing in situ hybridization and immunohistochemistry, we found that both ATRAP mRNA and the protein were widely distributed along the renal tubules from Bowman's capsules to the inner medullary collecting ducts. ATRAP mRNA was also detected in the glomeruli, vasculature, and interstitial cells. In all tubular cells, the ATRAP protein colocalized with the AT1 receptor. Finally, we found that the dietary salt depletion significantly decreased the renal expression of ATRAP as well as AT1 receptor. These findings show ATRAP to be abundantly and broadly distributed in nephron segments where the AT1 receptor is expressed. Furthermore, this is the first report demonstrating a substantial colocalization of ATRAP and AT1 receptor in vivo.