Regulation of glutamate transporter GLT-1 by MAGI-1.

Autor: Zou S; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA., Pita-Almenar JD, Eskin A
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2011 Jun; Vol. 117 (5), pp. 833-40. Date of Electronic Publication: 2011 Apr 19.
DOI: 10.1111/j.1471-4159.2011.07250.x
Abstrakt: 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.
(© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.)
Databáze: MEDLINE
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