Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18

• Published in: Nature (London) Vol. 410; no. 6824; pp. 84 - 88
• Main Authors: Rothstein, Jeffrey D, Lin, Chien-liang Glenn, Orlov, Irina, Ruggiero, Alicia M, Dykes-Hoberg, Margaret, Lee, Andy, Jackson, Mandy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.03.2001; Nature Publishing Group
• Subjects: Amino acid (excitatory) transporter 1; Amino Acid Transport System X-AG; Amino acids; Animals; aspartic acid transporter; ATP-Binding Cassette Transporters - metabolism; Biological and medical sciences; Biological Transport - drug effects; Brain; Brain - metabolism; Carrier Proteins - metabolism; Cell Line; Cloning, Molecular; Excitatory Amino Acid Transporter 3; Fundamental and applied biological sciences. Psychology; Glutamate Plasma Membrane Transport Proteins; Glutamic Acid - metabolism; GTRAP3-18 protein; Membrane Proteins - metabolism; Metabolisms and neurohumoral controls; Molecular Sequence Data; Neurology; Neurons; Nitrogen metabolism. Proteins. Glycoproteins. Nucleic acids. Collagen; Precipitin Tests; Protein Binding; Protein Kinase C - genetics; Protein Kinase C - metabolism; Proteins; Proteins - genetics; Proteins - metabolism; Rats; Recombinant Fusion Proteins - metabolism; Symporters; Tissue Distribution; Tretinoin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Tissue; Modulation; Excitatory aminoacid; Neurotransmitter; Gene expression; Glutamate; Carrier protein
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35065084

Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent l-glutamate/d, l-aspartate cell-membrane transport protein. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter. It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment. In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism. Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.