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Heteromeric Amino Acid Transporters in Brain: from Physiology to Pathology

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Abstract

In humans, more than 50 transporters are responsible for the traffic and balance of amino acids within and between cells and tissues, and half of them have been associated with disease [1]. Covering all common amino acids, Heteromeric Amino acid Transporters (HATs) are one class of such transporters. This review first highlights structural and functional studies that solved the atomic structure of HATs and revealed molecular clues on substrate interaction. Moreover, this review focuses on HATs that have a role in the central nervous system (CNS) and that are related to neurological diseases, including: (i) LAT1/CD98hc and its role in the uptake of branched chain amino acids trough the blood brain barrier and autism. (ii) LAT2/CD98hc and its potential role in the transport of glutamine between plasma and cerebrospinal fluid. (iii) y+LAT2/CD98hc that is emerging as a key player in hepatic encephalopathy. xCT/CD98hc as a potential therapeutic target in glioblastoma, and (iv) Asc-1/CD98hc as a potential therapeutic target in pathologies with alterations in NMDA glutamate receptors.

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Acknowledgements

We thank Baruch Kanner, who has guided our structural-functional studies of amino acid transporters over the last 30 years. Recent work in amino acid transporters in our lab has been supported by the Spanish Ministry of Science, Innovation and Universities (MSIU) (SAF2015-64869-R-FEDER, RTI2018-094211-B-I00) and the Fundació La Marató-TV3. We gratefully acknowledge institutional funding from MSIU to IRB Barcelona with the Centres of Excellence Severo Ochoa Award.

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  1. Institute for Research in Biomedicine. Institute of Science and Technology (BIST), 08028, Barcelona, Spain

    Ekaitz Errasti-Murugarren & Manuel Palacín

  2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 08028, Barcelona, Spain

    Ekaitz Errasti-Murugarren & Manuel Palacín

  3. Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain

    Manuel Palacín

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  1. Ekaitz Errasti-Murugarren
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  2. Manuel Palacín
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Correspondence to Ekaitz Errasti-Murugarren or Manuel Palacín.

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Special Issue: In Honor of Prof. Baruch Kanner.

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Errasti-Murugarren, E., Palacín, M. Heteromeric Amino Acid Transporters in Brain: from Physiology to Pathology. Neurochem Res 47, 23–36 (2022). https://doi.org/10.1007/s11064-021-03261-w

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  • DOI: https://doi.org/10.1007/s11064-021-03261-w

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