Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1

Fairweather, Stephen J., Broer, Angelika, O'Mara, Megan L. and Broer, Stefan (2012) Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1. Biochemical Journal, 446 1: 135-148. doi:10.1042/BJ20120307


Author Fairweather, Stephen J.
Broer, Angelika
O'Mara, Megan L.
Broer, Stefan
Title Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1
Formatted title
Intestinal peptidases form functional complexes with the neutral amino acid transporter B0AT1
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
1470-8728
Publication date 2012-08-15
Sub-type Article (original research)
DOI 10.1042/BJ20120307
Volume 446
Issue 1
Start page 135
End page 148
Total pages 14
Place of publication London, United Kingdom
Publisher Portland Press
Collection year 2013
Language eng
Formatted abstract
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 B0AT1 [broad neutral (0) amino acid transporter 1; SLC6A19 (solute carrier family 6 member 19)] in the intestine and by B0AT1 and B0AT3 (SLC6A18) in the kidney. Immunoprecipitation and Blue native electrophoresis of intestinal brush-border membrane proteins revealed that B0AT1 forms complexes with two peptidases, APN (aminopeptidase N/CD13) and ACE2 (angiotensin-converting enzyme 2). Physiological characterization of B0AT1 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 B0AT1 apparent substrate affinity, possibly by increasing the local substrate concentration. These results provide evidence for the existence of B0AT1-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.
Keyword Aminopeptidase N
Angiotensin-converting enzyme 2 (ACE2)
Broad neutral (0) amino acid transporter 1 (B0AT1)
Brush-border membrane
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 02 Oct 2012, 15:54:48 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences