title: The availability of surface GABA B receptors is independent of gamma-aminobutyric acid but controlled by glutamate in central neurons.
abstract: 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 gamma-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.
authors.affiliation: Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Karina J
authors.initials: KJ
authors.lastname: Vargas
authors.forename: Miho
authors.initials: M
authors.lastname: Terunuma
authors.forename: Judith A
authors.initials: JA
authors.lastname: Tello
authors.forename: Menelas N
authors.initials: MN
authors.lastname: Pangalos
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
authors.forename: Andrés
authors.initials: A
authors.lastname: Couve
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D034284:Dynamin I / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002966:Clathrin; D018080:Receptors, GABA-B; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D046988:Proteasome Endopeptidase Complex; D034284:Dynamin I