Danilczyk Ursula, Sarao Renu, Remy Christine, Benabbas Chahira, Stange Gerti, Richter Andreas, Arya Sudha, Pospisilik J Andrew, Singer Dustin, Camargo Simone M R, Makrides Victoria, Ramadan Tamara, Verrey Francois, Wagner Carsten A, Penninger Josef M
IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, A-1030, Vienna, Austria.
Nature. 2006 Dec 21;444(7122):1088-91. doi: 10.1038/nature05475. Epub 2006 Dec 13.
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. A gene encoding a homologue to ACE2, termed collectrin (Tmem27), has been identified in immediate proximity to the ace2 locus. 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.
血管紧张素转换酶2(ACE2)是肾素血管紧张素系统的一种调节因子,参与哺乳动物的急性肺衰竭、心血管功能及严重急性呼吸综合征(SARS)感染。在紧邻ace2基因座处已鉴定出一个编码与ACE2同源物的基因,称为collectrin(Tmem27)。Collectrin在体内的功能尚不清楚。在此我们报告,小鼠中collectrin的靶向破坏导致肾氨基酸摄取严重缺陷,这是由于肾脏顶端氨基酸转运体下调所致。Collectrin与多种顶端转运体相关联,并定义了一组新的肾脏氨基酸转运体。Collectrin在非洲爪蟾卵母细胞和Madin-Darby犬肾(MDCK)细胞中的表达增强了转运体B(0)AT1介导的氨基酸转运。这些数据确定Collectrin是肾氨基酸摄取的关键调节因子。