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Intestinal peptidases form functional complexes with the neutral amino acid transporter BᴼAT1

Fairweather, Stephen J; Bröer, Angelika; O’Mara, Megan L; Bröer, Stefan

Description

The brush-border membrane of the small intestine and kidney proximal tubule are the major sites for the absorption and re-absorption of nutrients in the body respectively. Transport of amino acids is mediated through the action of numerous secondary active transporters. In the mouse, neutral amino acids are transported by BᴼAT1 [broad neutral (ᴼ) amino acid transporter 1; SLC6A19 (solute carrier family 6 member 19)] in the intestine and by BᴼAT1 and BᴼAT3 (SLC6A18) in the...[Show more]

dc.contributor.authorFairweather, Stephen J
dc.contributor.authorBröer, Angelika
dc.contributor.authorO’Mara, Megan L
dc.contributor.authorBröer, Stefan
dc.date.accessioned2014-08-18T23:51:19Z
dc.date.available2014-08-18T23:51:19Z
dc.identifier.issn0264-6021
dc.identifier.urihttp://hdl.handle.net/1885/11953
dc.description.abstractThe brush-border membrane of the small intestine and kidney proximal tubule are the major sites for the absorption and re-absorption of nutrients in the body respectively. Transport of amino acids is mediated through the action of numerous secondary active transporters. In the mouse, neutral amino acids are transported by BᴼAT1 [broad neutral (ᴼ) amino acid transporter 1; SLC6A19 (solute carrier family 6 member 19)] in the intestine and by BᴼAT1 and BᴼAT3 (SLC6A18) in the kidney. Immunoprecipitation and Blue native electrophoresis of intestinal brush-border membrane proteins revealed that BᴼAT1 forms complexes with two peptidases, APN (aminopeptidase N/CD13)and ACE2 (angiotensin-converting enzyme 2). Physiological characterization of BᴼAT1 expressed together with these peptidases in Xenopus laevis oocytes revealed that APN increased the substrate affinity of the transporter up to 2.5-fold and also increased its surface expression (Vmax). Peptide competition experiments, in silico modelling and site-directed mutagenesis of APN suggest that the catalytic site of the peptidase is involved in the observed changes of BᴼAT1 apparent substrate affinity, possibly by increasing the local substrate concentration. These results provide evidence for the existence of BᴼAT1-containing digestive complexes in the brush-border membrane, interacting differentially with various peptidases, and responding to the dynamic needs of nutrient absorption in the intestine and kidney.
dc.description.sponsorshipThis study was supported by the National Health and Medical Research Council [grant number 525415].
dc.format14 pages
dc.publisherPortland Press
dc.rights© 2012 The Author(s)/The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.sourceBiochemical Journal 446. 1 (2012): 135-148
dc.subjectaminopeptidase
dc.subjectN
dc.subjectangiotensin
dc.subjectconverting
dc.subjectenzyme
dc.subject2
dc.subjectACE2
dc.subjectbroad
dc.subjectneutral
dc.subject(ᴼ)
dc.subjectamino
dc.subjectacid
dc.subjecttransporter
dc.subject1
dc.subject(BᴼAT1)
dc.subjectbrush
dc.subjectborder
dc.subjectmembrane
dc.subjectnutrient
dc.subjectabsorption
dc.subjectprotein
dc.subjectcomplex
dc.titleIntestinal peptidases form functional complexes with the neutral amino acid transporter BᴼAT1
dc.typeJournal article
local.identifier.citationvolume446
dcterms.dateAccepted2012-06-07
dc.date.issued2012-08-15
local.identifier.absfor060110 - Receptors and Membrane Biology
local.identifier.absfor060104 - Cell Metabolism
local.identifier.ariespublicationf5625xPUB2185
local.identifier.ariespublicationu8801298xPUB84
local.publisher.urlhttp://www.portlandpress.com/
local.type.statusPublished Version
local.contributor.affiliationBröer, Stefan, Research School of Biology, Australian National University
local.contributor.affiliationFairweather, Stephen J., Research School of Biology, Australian National University
local.contributor.affiliationBröer, Angelika, Research School of Biology, Australian National University
dc.relationhttp://purl.org/au-research/grants/nhmrc/525415
local.identifier.essn1470-8728
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage135
local.bibliographicCitation.lastpage148
local.identifier.doi10.1042/BJ20120307
local.identifier.absseo920105 - Digestive System Disorders
dc.date.updated2015-12-10T11:50:14Z
local.identifier.scopusID2-s2.0-84864742367
local.identifier.thomsonID000307626300013
CollectionsANU Research Publications

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