Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem J
2004 Feb 01;377Pt 3:665-74. doi: 10.1042/BJ20030956.
Show Gene links
Show Anatomy links
Cystinuria-specific rBAT(R365W) mutation reveals two translocation pathways in the amino acid transporter rBAT-b0,+AT.
Pineda M
,
Wagner CA
,
Bröer A
,
Stehberger PA
,
Kaltenbach S
,
Gelpí JL
,
Martín Del Río R
,
Zorzano A
,
Palacín M
,
Lang F
,
Bröer S
.
???displayArticle.abstract???
Apical reabsorption of dibasic amino acids and cystine in kidney is mediated by the heteromeric amino acid antiporter rBAT/b(0,+)AT (system b(0,+)). Mutations in rBAT cause cystinuria type A, whereas mutations in b(0,+)AT cause cystinuria type B. b(0,+)AT is the catalytic subunit, whereas it is believed that rBAT helps the routing of the rBAT/b(0,+)AT heterodimeric complex to the plasma membrane. In the present study, we have functionally characterized the cystinuria-specific R365W (Arg(365)-->Trp) mutation of human rBAT, which in addition to a trafficking defect, alters functional properties of the b(0,+) transporter. In oocytes, where human rBAT interacts with the endogenous b(0,+)AT subunit to form an active transporter, the rBAT(R365W) mutation caused a defect of arginine efflux without altering arginine influx or apparent affinities for intracellular or extracellular arginine. Transport of lysine or leucine remained unaffected. In HeLa cells, functional expression of rBAT(R365W)/b(0,+)AT was observed only at the permissive temperature of 33 degrees C. Under these conditions, the mutated transporter showed 50% reduction of arginine influx and a similar decreased accumulation of dibasic amino acids. Efflux of arginine through the rBAT(R365W)/b(0,+)AT holotransporter was completely abolished. This supports a two-translocation-pathway model for antiporter b(0,+), in which the efflux pathway in the rBAT(R365W)/b(0,+)AT holotransporter is defective for arginine translocation or dissociation. This is the first direct evidence that mutations in rBAT may modify transport properties of system b(0,+).
Albers,
Mutations in the SLC3A1 gene in cystinuric patients: frequencies and identification of a novel mutation.
1999, Pubmed
Albers,
Mutations in the SLC3A1 gene in cystinuric patients: frequencies and identification of a novel mutation.
1999,
Pubmed
Bauch,
Apical heterodimeric cystine and cationic amino acid transporter expressed in MDCK cells.
2002,
Pubmed
,
Xenbase
Bertran,
Expression cloning of a cDNA from rabbit kidney cortex that induces a single transport system for cystine and dibasic and neutral amino acids.
1992,
Pubmed
,
Xenbase
Bertran,
Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Bröer,
Structure-function relationships of heterodimeric amino acid transporters.
2002,
Pubmed
Bröer,
Expression of Na+-independent isoleucine transport activity from rat brain in Xenopus laevis oocytes.
1994,
Pubmed
,
Xenbase
Busch,
Opposite directed currents induced by the transport of dibasic and neutral amino acids in Xenopus oocytes expressing the protein rBAT.
1994,
Pubmed
,
Xenbase
Calonge,
Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine.
1994,
Pubmed
,
Xenbase
Chillarón,
Heteromeric amino acid transporters: biochemistry, genetics, and physiology.
2001,
Pubmed
Chillarón,
Obligatory amino acid exchange via systems bo,+-like and y+L-like. A tertiary active transport mechanism for renal reabsorption of cystine and dibasic amino acids.
1996,
Pubmed
,
Xenbase
Chillarón,
An intracellular trafficking defect in type I cystinuria rBAT mutants M467T and M467K.
1997,
Pubmed
,
Xenbase
Coady,
Electrogenic amino acid exchange via the rBAT transporter.
1994,
Pubmed
,
Xenbase
Dello Strologo,
Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification.
2002,
Pubmed
Denning,
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.
1992,
Pubmed
,
Xenbase
Devés,
Surface antigen CD98(4F2): not a single membrane protein, but a family of proteins with multiple functions.
2000,
Pubmed
Feliubadaló,
Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT.
1999,
Pubmed
Fernández,
rBAT-b(0,+)AT heterodimer is the main apical reabsorption system for cystine in the kidney.
2002,
Pubmed
Font,
Functional analysis of mutations in SLC7A9, and genotype-phenotype correlation in non-Type I cystinuria.
2001,
Pubmed
Gasparini,
Molecular genetics of cystinuria: identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity.
1995,
Pubmed
Meier,
Activation of system L heterodimeric amino acid exchangers by intracellular substrates.
2002,
Pubmed
,
Xenbase
Mosckovitz,
Membrane topology of the rat kidney neutral and basic amino acid transporter.
1994,
Pubmed
,
Xenbase
Palacín,
The molecular bases of cystinuria and lysinuric protein intolerance.
2001,
Pubmed
Palmieri,
Functional properties of purified and reconstituted mitochondrial metabolite carriers.
1993,
Pubmed
Peter,
Cysteine residues in the C-terminus of the neutral- and basic-amino-acid transporter heavy-chain subunit contribute to functional properties of the system b(0,+)-type amino acid transporter.
2000,
Pubmed
,
Xenbase
Pfeiffer,
Luminal heterodimeric amino acid transporter defective in cystinuria.
1999,
Pubmed
,
Xenbase
Rajan,
Differential influence of the 4F2 heavy chain and the protein related to b(0,+) amino acid transport on substrate affinity of the heteromeric b(0,+) amino acid transporter.
2000,
Pubmed
Reig,
The light subunit of system b(o,+) is fully functional in the absence of the heavy subunit.
2002,
Pubmed
Restrepo,
A novel method to differentiate between ping-pong and simultaneous exchange kinetics and its application to the anion exchanger of the HL60 cell.
1992,
Pubmed
Saadi,
Molecular genetics of cystinuria: mutation analysis of SLC3A1 and evidence for another gene in type I (silent) phenotype.
1998,
Pubmed
,
Xenbase
Stegen,
Swelling-induced taurine release without chloride channel activity in Xenopus laevis oocytes expressing anion channels and transporters.
2000,
Pubmed
,
Xenbase
Torras-Llort,
Sequential amino acid exchange across b(0,+)-like system in chicken brush border jejunum.
2001,
Pubmed
Verrey,
New glycoprotein-associated amino acid transporters.
1999,
Pubmed
Verrey,
Glycoprotein-associated amino acid exchangers: broadening the range of transport specificity.
2000,
Pubmed
Wagner,
The use of Xenopus laevis oocytes for the functional characterization of heterologously expressed membrane proteins.
2000,
Pubmed
,
Xenbase
Wagner,
Function and structure of heterodimeric amino acid transporters.
2001,
Pubmed
Wang,
Oligomeric structure of a renal cystine transporter: implications in cystinuria.
1995,
Pubmed
,
Xenbase
Ward,
Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins.
1994,
Pubmed
Wells,
Cloning of a rat kidney cDNA that stimulates dibasic and neutral amino acid transport and has sequence similarity to glucosidases.
1992,
Pubmed
,
Xenbase