A protein complex in the brush-border membrane explains a Hartnup disorder allele

FASEB J. 2008 Aug;22(8):2880-7. doi: 10.1096/fj.08-107300. Epub 2008 Apr 18.


Protein absorption in the intestine is mediated by proteases and brush-border peptidases together with peptide and amino acid transporters. Neutral amino acids are generated by a variety of aminopeptidases and carboxypeptidases and are subsequently taken up by the amino acid transporter B(0)AT1 (SLC6A19), which is mutated in Hartnup disorder. Coexpression of B(0)AT1 together with the brush-border carboxypeptidase angiotensin-converting enzyme 2 (ACE2) in Xenopus laevis oocytes led to a dramatic increase of transporter expression at the oocyte surface. Other members of the SLC6 family were not stimulated by coexpression with ACE2. Addition of a peptide containing a carboxyterminal leucine residue to ACE2- and B(0)AT1-coexpressing oocytes caused inward currents due to Na(+)-leucine cotransport, demonstrating the formation of a metabolic complex. Coexpression of the Hartnup disorder causing mutation B(0)AT1(R240Q) showed reduced interaction with ACE2 and its renal paralogue collectrin. This would result in reduced surface expression in both kidney and intestine, thereby explaining the onset of the disorder in individuals carrying this mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Amino Acid Transport Systems, Neutral / chemistry
  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Female
  • Hartnup Disease / genetics*
  • Hartnup Disease / metabolism*
  • Humans
  • In Vitro Techniques
  • Intestine, Small / metabolism
  • Kidney / metabolism
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microvilli / metabolism*
  • Models, Molecular
  • Multiprotein Complexes
  • Mutation
  • Oocytes / metabolism
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Xenopus laevis


  • Amino Acid Transport Systems, Neutral
  • CLTRN protein, human
  • DNA Primers
  • Membrane Glycoproteins
  • Multiprotein Complexes
  • Recombinant Proteins
  • SLC6A19 protein, human
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2