NDLI: Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3.

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Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3.

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Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kuba, Keiji Verrey, Francois Chesnov, Serge Romeo, Elisa Huggel, Katja Camargo, Simone M. R. Singer, Dustin Danilczyk, Ursula Penninger, Josef M. Caron, Marc G.
Description	Author Affiliation: Singer D ( Institute of Physiology and Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland.)
Abstract	The orphan transporter Slc6a18 (XT2) is highly expressed at the luminal membrane of kidney proximal tubules and displays approximately 50% identity with Slc6a19 (B(0)AT1), 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(-)-de pend ent 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 beta-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-de pend ent neutral amino acid transporter that we propose to rename B(0)AT3.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	30
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-07-24
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amino Acid Transport Systems, Neutral Metabolism Membrane Glycoproteins Membrane Transport Proteins Genetics Peptidyl-Dipeptidase A Amino Acids Urine Animals Biological Transport Blood Pressure Gene Expression Physiology Mice Mice, Inbred C57BL Mice, Knockout Oocytes Plasma Membrane Neurotransmitter Transport Proteins Respiration Substrate Specificity Xenopus Laevis Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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