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The Availability of Surface GABAB Receptors Is Independent of γ-Aminobutyric Acid but Controlled by Glutamate in Central Neurons

The efficacy of synaptic transmission depends on the availability of ionotropic and metabotropic neurotransmitter receptors at the plasma membrane, but the contribution of the endocytic and recycling pathways in the regulation of γ-aminobutyric acid type B (GABA B ) receptors remains controversial....

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Published in:The Journal of biological chemistry 2008-09, Vol.283 (36), p.24641
Main Authors: Karina J. Vargas, Miho Terunuma, Judith A. Tello, Menelas N. Pangalos, Stephen J. Moss, Andrés Couve
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container_issue 36
container_start_page 24641
container_title The Journal of biological chemistry
container_volume 283
creator Karina J. Vargas
Miho Terunuma
Judith A. Tello
Menelas N. Pangalos
Stephen J. Moss
Andrés Couve
description The efficacy of synaptic transmission depends on the availability of ionotropic and metabotropic neurotransmitter receptors at the plasma membrane, but the contribution of the endocytic and recycling pathways in the regulation of γ-aminobutyric acid type B (GABA B ) receptors remains controversial. To understand the mechanisms that regulate the abundance of GABA B receptors, we have studied their turnover combining surface biotin labeling and a microscopic immunoendocytosis assay in hippocampal and cortical neurons. We report that internalization of GABA B receptors is agonist-independent. We also demonstrate that receptors endocytose in the cell body and dendrites but not in axons. Additionally, we show that GABA B receptors endocytose as heterodimers via clathrin- and dynamin-1-dependent mechanisms and that they recycle to the plasma membrane after endocytosis. More importantly, we show that glutamate decreases the levels of cell surface receptors in a manner dependent on an intact proteasome pathway. These observations indicate that glutamate and not GABA controls the abundance of surface GABA B receptors in central neurons, consistent with their enrichment at glutamatergic synapses.
doi_str_mv 10.1074/jbc.M802419200
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title The Availability of Surface GABAB Receptors Is Independent of γ-Aminobutyric Acid but Controlled by Glutamate in Central Neurons
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