TY - JOUR
T1 - Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins
AU - Jackson, Mandy
AU - Song, Wei
AU - Liu, Mu Ya
AU - Jin, Lin
AU - Dykes-Hoberg, Margaret
AU - Lin, Chien Liang G
AU - Bowers, William J.
AU - Federoff, Howard J.
AU - Sternweis, Paul C.
AU - Rothstein, Jeffrey D.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - 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.
AB - 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.
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U2 - 10.1038/35065091
DO - 10.1038/35065091
M3 - Letter
C2 - 11242047
AN - SCOPUS:0035282328
SN - 0028-0836
VL - 410
SP - 89
EP - 93
JO - Nature
JF - Nature
IS - 6824
ER -