Essential role for collectrin in renal amino acid transport
Essential role for collectrin in renal amino acid transport
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DOI：
10.1038/nature05475
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发表时间：
2006-12-21
期刊：
影响因子：
64.8
通讯作者：
Penninger, Josef M.
中科院分区：
文献类型：
--
作者：
Danilczyk, Ursula;Sarao, Renu;Penninger, Josef M.
血管紧张素转换酶2（ACE 2）是涉及哺乳动物的急性肺衰竭、心血管功能和严重急性呼吸综合征（SARS）感染的肾素血管紧张素系统的调节剂（1-3）。编码ACE 2同源物的基因，称为collectrin（Tmem 27），已被鉴定为紧邻ace 2基因座（4）。collectrin的体内功能尚不清楚。在这里，我们报告，有针对性的破坏collectrin在小鼠的结果在肾脏氨基酸摄取严重缺陷，由于在肾脏中的顶端氨基酸转运蛋白下调。Collectrin与多种顶端转运蛋白相关，并定义了一组新的肾脏氨基酸转运蛋白。在非洲爪蟾卵母细胞和Madin-Darby犬肾（MDCK）细胞中表达collectrin可增强转运蛋白B-0 AT 1的氨基酸转运。这些数据确定collectrin作为肾脏氨基酸摄取的关键调节因子。
Angiotensin-converting enzyme 2 (ACE2) is a regulator of the renin angiotensin system involved in acute lung failure, cardiovascular functions and severe acute respiratory syndrome (SARS) infections in mammals(1-3). A gene encoding a homologue to ACE2, termed collectrin (Tmem27), has been identified in immediate proximity to the ace2 locus(4). The in vivo function of collectrin was unclear. Here we report that targeted disruption of collectrin in mice results in a severe defect in renal amino acid uptake owing to downregulation of apical amino acid transporters in the kidney. Collectrin associates with multiple apical transporters and defines a novel group of renal amino acid transporters. Expression of collectrin in Xenopus oocytes and Madin-Darby canine kidney (MDCK) cells enhances amino acid transport by the transporter B-0 AT1. These data identify collectrin as a key regulator of renal amino acid uptake.