Errasti-Murugarren Ekaitz, Palacín Manuel
Institute for Research in Biomedicine. Institute of Science and Technology (BIST), 08028, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 08028, Barcelona, Spain.
Neurochem Res. 2022 Jan;47(1):23-36. doi: 10.1007/s11064-021-03261-w. Epub 2021 Feb 19.
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) yLAT2/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.
在人类中，50多种转运蛋白负责细胞和组织内及组织间氨基酸的运输和平衡，其中一半与疾病有关[1]。异源氨基酸转运体（HATs）涵盖所有常见氨基酸，是这类转运蛋白中的一类。本综述首先重点介绍了那些解析了HATs原子结构并揭示了底物相互作用分子线索的结构和功能研究。此外，本综述聚焦于在中枢神经系统（CNS）中发挥作用且与神经疾病相关的HATs，包括：（i）LAT1/CD98hc及其在通过血脑屏障摄取支链氨基酸和自闭症中的作用。（ii）LAT2/CD98hc及其在血浆和脑脊液之间运输谷氨酰胺中的潜在作用。（iii）yLAT2/CD98hc正成为肝性脑病的关键因素。xCT/CD98hc作为胶质母细胞瘤的潜在的潜在治疗靶点，以及（iv）Asc-1/CD98hc作为NMDA谷氨酸受体改变相关疾病的潜在治疗靶点。
