Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins

Mandy Jackson, Wei Song, Mu Ya Liu, Lin Jin, Margaret Dykes-Hoberg, Chien Liang G Lin, William J. Bowers, Howard J. Federoff, Paul C. Sternweis, Jeffrey D. Rothstein

Research output: Contribution to journalLetter

194 Scopus citations

Abstract

Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system and is removed from the synaptic cleft by sodium-dependent glutamate transporters. To date, five distinct glutamate transporters have been cloned from animal and human tissue: GLAST (EAAT1), GLT-1 (EAAT2), EAAC1 (EAAT3), EAAT4, and EAAT5 (refs 1, 2, 3, 4, 5). GLAST and GLT-1 are localized primarily in astrocytes6, 7, whereas EAAC1 (refs 8, 9), EAAT4 (refs 9, 10, 11) and EAAT5 (ref. 5) are neuronal. Studies of EAAT4 and EAAC1 indicate an extrasynaptic localization on perisynaptic membranes that are near release sites8-10. This localization facilitates rapid glutamate binding, and may have a role in shaping the amplitude of postsynaptic responses in densely packed cerebellar terminals12-15. We have used a yeast two-hybrid screen to identify interacting proteins that may be involved in regulating EAAT4-the glutamate transporter expressed predominately in the cerebellum-or in targeting and/or anchoring or clustering the transporter to the target site. Here we report the identification and characterization of two proteins, GTRAP41 and GTRAP48 (for glutamate transporter EAAT4 associated protein) that specifically interact with the intracellular carboxy-terminal domain of EAAT4 and modulate its glutamate transport activity.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalNature
Volume410
Issue number6824
DOIs
StatePublished - Mar 1 2001

ASJC Scopus subject areas

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    Jackson, M., Song, W., Liu, M. Y., Jin, L., Dykes-Hoberg, M., Lin, C. L. G., Bowers, W. J., Federoff, H. J., Sternweis, P. C., & Rothstein, J. D. (2001). Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins. Nature, 410(6824), 89-93. https://doi.org/10.1038/35065091