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The ancillary proteins of HATs: SLC3 family of amino acid transporters

  • The ABC of Solute Carriers
  • Guest Editor: Matthias A. Hediger
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Abstract

The heteromeric amino acid transporters (HATs) are composed of a light and a heavy subunit linked by a disulfide bridge. The heavy subunits are the SLC3 members (rBAT and 4F2hc), whereas the light subunits are members of the SLC7 family of amino acid transporters. SLC3 proteins are type II membrane glycoproteins (i.e., one single transmembrane domain and the C-terminus located outside the cell) with a bulky extracellular domain that shows homology with α-glucosidases. rBAT heterodimerizes with b0,+AT (SLC7A9) constituting the amino acid transport b0,+, the main system responsible for the apical reabsorption of cystine in kidney. The defect in this system causes cystinuria, the most common primary inherited aminoaciduria. 4F2hc subserves various amino acid transport systems by dimerization with different SLC7 proteins. The main role of SLC3 proteins is to help routing of the holotransporter to the plasma membrane. A working model for the biogenesis of HATs based on recent data on the rBAT/b0,+AT heterodimeric complex is presented. 4F2hc is a multifunctional protein, and in addition to its role in amino acid transport, it may be involved in other cellular functions. Studies on two SLC7 members (Asc-2 and AGT1) demonstrate heterodimerization with unknown heavy subunits.

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Acknowledgements

We thank Robin Rycroft for editing the manuscript. The laboratory of M.P. is supported by the Spanish Dirección General de Investigación Científica y Técnica Research Grant PM 99/0172, the Comissionat per a Universitats i Recerca and Grant 2001SGR00118 from the Generalitat de Catalunya (Spain), and the Instituto de Salud Carlos III network G03/054 (Spain). The laboratory of Y.K. is supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Society for the Promotion of Science, and the Promotion and Mutual Aid Corporation for Private Schools of Japan.

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  1. Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Parc Cientìfic de Barcelona, Avda. Diagonal 645, 08028, Barcelona, Spain

    Manuel Palacín

  2. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, 181-8611, Tokyo, Japan

    Yoshikatsu Kanai

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Correspondence to Manuel Palacín.

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Palacín, M., Kanai, Y. The ancillary proteins of HATs: SLC3 family of amino acid transporters. Pflugers Arch - Eur J Physiol 447, 490–494 (2004). https://doi.org/10.1007/s00424-003-1062-7

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  • DOI: https://doi.org/10.1007/s00424-003-1062-7

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