The heteromeric amino acid transporter glycoprotein subunits rBAT and 4F2hc (heavy chains) form, with different catalytic subunits (light chains), functional heterodimers that are covalently stabilized by a disulphide bridge. Whereas rBAT associates with b0,+AT to form the cystine and cationic amino acid transporter defective in cystinuria, 4F2hc associates with other homologous light chains, for instance with LAT1 to form a system L neutral amino acid transporter. To identify within the heavy chains the domain(s) involved in recognition of and functional interaction with partner light chains, chimaeric and truncated forms of rBAT and 4F2hc were co-expressed in Xenopus laevis oocytes with b0,+AT or LAT1. Heavy chain–light chain association was analysed by co-immunoprecipitation, and transport function was tested by tracer uptake experiments. The results indicate that the cytoplasmic tail and transmembrane domain of rBAT together play a dominant role in selective functional interaction with b0,+AT, whereas the extracellular domain of rBAT appears to facilitate specifically L-cystine uptake. For 4F2hc, functional interaction with LAT1 was mediated by the N-terminal part, comprising cytoplasmic tail, transmembrane segment and neck, even in the absence of the extracellular domain. Alternatively, functional association with LAT1 was also supported by the extracellular part of 4F2hc comprising neck and glycosidase-like domain linked to the complementary part of rBAT. In conclusion, the cytoplasmic tail and the transmembrane segment together play a determinant role for the functional interaction of rBAT with b0,+AT, whereas either cytoplasmic or extracellular glycosidase-like domains are dispensable for the functional interaction of 4F2hc with LAT1.
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Research Article|
May 24 2005
Heterodimeric amino acid transporter glycoprotein domains determining functional subunit association
Raffaella FRANCA;
Raffaella FRANCA
1Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Emilija VELJKOVIC;
Emilija VELJKOVIC
1Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Stefan WALTER;
Stefan WALTER
1Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Carsten A. WAGNER;
Carsten A. WAGNER
1Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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François VERREY
François VERREY
1
1Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
1To whom correspondence should be addressed (email verrey@access.unizh.ch).
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Publisher: Portland Press Ltd
Received:
January 04 2005
Accepted:
January 28 2005
Accepted Manuscript online:
January 28 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 388 (2): 435–443.
Article history
Received:
January 04 2005
Accepted:
January 28 2005
Accepted Manuscript online:
January 28 2005
Citation
Raffaella FRANCA, Emilija VELJKOVIC, Stefan WALTER, Carsten A. WAGNER, François VERREY; Heterodimeric amino acid transporter glycoprotein domains determining functional subunit association. Biochem J 1 June 2005; 388 (2): 435–443. doi: https://doi.org/10.1042/BJ20050021
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