Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3

Dustin Singer, Simone M.R. Camargo, Katja Huggel, Elisa Romeo, Ursula Danilczyk, Keiji Kuba, Serge Chesnov, Marc G. Caron, Josef M. Penninger, Francois Verrey

研究成果: ジャーナルへの寄稿学術誌査読

45 被引用数 (Scopus)

抄録

The orphan transporter Slc6a18 (XT2) is highly expressed at the luminal membrane of kidney proximal tubules and displays ∼50% identity with Slc6a19 (B0AT1), which is the main neutral amino acid transporter in both kidney and small intestine. As yet, the amino acid transport function of XT2 has only been experimentally supported by the urinary glycine loss observed in xt2 null mice. We report here that in Xenopus laevis oocytes, co-expressed ACE2 (angiotensin-converting enzyme 2) associates with XT2 and reveals its function as a Na+ - and Cl--dependent neutral amino acid transporter. In contrast to its association with ACE2 observed in Xenopus laevis oocytes, our experiments with ace2 and collectrin null mice demonstrate that in vivo it is Collectrin, a smaller homologue of ACE2, that is required for functional expression of XT2 in kidney. To assess the function of XT2 in vivo, we reanalyzed its knock-out mouse model after more than 10 generations of backcrossing into C57BL/6 background. In addition to the previously published glycinuria, we observed a urinary loss of several other amino acids, in particular β-branched and small neutral ones. Using telemetry, we confirmed the previously described link of XT2 absence with hypertension but only in physically restrained animals. Taken together, our data indicate that the formerly orphan transporter XT2 functions as a sodium and chloride-dependent neutral amino acid transporter that we propose to rename B0AT3.

本文言語英語
ページ(範囲)19953-19960
ページ数8
ジャーナルJournal of Biological Chemistry
284
30
DOI
出版ステータス出版済み - 7月 24 2009
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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