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

Autor: John Edward Rasko, Stefan Bröer, Jessica M. Vanslambrouck, Angelika Bröer, Sonja Kowalczuk, Nadine Tietze
Rok vydání: 2008
Předmět:
Models
Molecular
Peptide
Biology
In Vitro Techniques
Peptidyl-Dipeptidase A
Kidney
Biochemistry
Aminopeptidase
Hartnup disease
03 medical and health sciences
Mice
Xenopus laevis
0302 clinical medicine
Intestine
Small
Genetics
medicine
Animals
Humans
Amino acid transporter
Molecular Biology
Alleles
030304 developmental biology
DNA Primers
chemistry.chemical_classification
0303 health sciences
Membrane Glycoproteins
Base Sequence
Microvilli
Kidney metabolism
Hartnup Disease
medicine.disease
Molecular biology
Carboxypeptidase
Recombinant Proteins
Amino acid
Amino Acid Transport Systems
Neutral
chemistry
Amino Acid Substitution
Multiprotein Complexes
Mutation
biology.protein
Oocytes
Female
Angiotensin-Converting Enzyme 2
Leucine
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Biotechnology
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 22(8)
ISSN: 1530-6860
Popis: 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.
Databáze: OpenAIRE
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