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Regulation of glutamate transporter GLT‐1 by MAGI‐1
Author(s) -
Zou Shengwei,
PitaAlmenar Juan D.,
Eskin Arnold
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07250.x
Subject(s) - glutamate receptor , immunoprecipitation , glutamate aspartate transporter , microbiology and biotechnology , biology , gene knockdown , transporter , biochemistry , small interfering rna , chemistry , rna , metabotropic glutamate receptor , receptor , gene , apoptosis
J. Neurochem. (2011) 117 , 833–840. Abstract The sodium‐dependent glutamate transporter, glutamate transporter subtype 1 (GLT‐1) is one of the main glutamate transporters in the brain. GLT‐1 contains a COOH‐terminal sequence similar to one in an isoform of Slo1 K + channel protein previously shown to bind MAGI‐1 (membrane‐associated guanylate kinase with inverted orientation protein‐1). MAGI‐1 is a scaffold protein which allows the formation of complexes between certain transmembrane proteins, actin‐binding proteins, and other regulatory proteins. The glutathione S ‐transferase pull‐down assay demonstrated that MAGI‐1 was a binding partner of GLT‐1. The interaction between MAGI‐1 and GLT‐1 was confirmed by co‐immunoprecipitation. Immunofluorescence of MAGI‐1 and GLT‐1 demonstrated that the distribution of MAGI‐1 and GLT‐1 overlapped in astrocytes. Co‐expression of MAGI‐1 with GLT‐1 in C6 Glioma cells resulted in a significant reduction in the surface expression of GLT‐1, as assessed by cell‐surface biotinylation. On the other hand, partial knockdown of endogenous MAGI‐1 expression by small interfering RNA in differentiated cultured astrocytes increased glutamate uptake and the surface expression of endogenous GLT‐1. Knockdown of MAGI‐1 increased dihydrokainate‐sensitive, Na + ‐dependent glutamate uptake, indicating that MAGI‐1 regulates GLT‐1 mediated glutamate uptake. These data suggest that MAGI‐1 regulates surface expression of GLT‐1 and the level of glutamate in the hippocampus.