Verrey François, Singer Dustin, Ramadan Tamara, Vuille-dit-Bille Raphael N, Mariotta Luca, Camargo Simone M R
Institute of Physiology, University of Zürich, Switzerland.
Pflugers Arch. 2009 May;458(1):53-60. doi: 10.1007/s00424-009-0638-2. Epub 2009 Jan 28.
Near complete reabsorption of filtered amino acids is a main specialized transport function of the kidney proximal tubule. This evolutionary conserved task is carried out by a subset of luminal and basolateral transporters that together form the transcellular amino acid transport machinery similar to that of small intestine. A number of other amino acid transporters expressed in the basolateral membrane of proximal kidney tubule cells subserve either specialized metabolic functions, such as the production of ammonium, or are part of the cellular housekeeping equipment. A new finding is that the luminal Na(+)-dependent neutral amino acid transporters of the SLC6 family require an associated protein for their surface expression as shown for the Hartnup transporter B(0)AT1 (SLC6A19) and suggested for the L: -proline transporter SIT1 (IMINO(B), SLC6A20) and for B(0)AT3 (XT2, SLC6A18). This accessory subunit called collectrin (TMEM27) is homologous to the transmembrane anchor region of the renin-angiotensin system enzyme ACE2 that we have shown to function in small intestine as associated subunit of the luminal SLC6 transporters B(0)AT1 and SIT1. Some mutations of B(0)AT1 differentially interact with these accessory subunits, providing an explanation for differential intestinal phenotypes among Hartnup patients. The basolateral efflux of numerous amino acids from kidney tubular cells is mediated by heteromeric amino acid transporters that function as obligatory exchangers. Thus, other transporters within the same membrane need to mediate the net efflux of exchange substrates, controlling thereby the net basolateral amino transport and thus the intracellular amino acid concentration.
滤过氨基酸的近乎完全重吸收是肾近端小管的一项主要特殊转运功能。这一进化上保守的任务由一组管腔侧和基底外侧转运体完成，它们共同构成了类似于小肠的跨细胞氨基酸转运机制。在近端肾小管细胞基底外侧膜表达的许多其他氨基酸转运体，要么承担特殊的代谢功能，如铵的产生，要么是细胞内维持功能的一部分。一项新发现是，SLC6家族的管腔侧Na⁺依赖性中性氨基酸转运体需要一种相关蛋白来实现其表面表达，如对Hartnup转运体B(0)AT1（SLC6A19）所示，并且对L-脯氨酸转运体SIT1（IMINO(B)，SLC6A20）和B(0)AT3（XT2，SLC6A18）也有类似推测。这种称为collectrin（TMEM27）的辅助亚基与肾素-血管紧张素系统酶ACE2的跨膜锚定区域同源，我们已证明ACE2在小肠中作为管腔侧SLC6转运体B(0)AT1和SIT1的相关亚基发挥作用。B(0)AT1的一些突变与这些辅助亚基存在差异相互作用，这为Hartnup病患者之间不同的肠道表型提供了解释。肾小管细胞中多种氨基酸的基底外侧流出由异源氨基酸转运体介导，这些转运体作为强制性交换体发挥作用。因此，同一膜内的其他转运体需要介导交换底物的净流出，从而控制基底外侧氨基酸的净转运，进而控制细胞内氨基酸浓度。
