2004
DOI: 10.1074/jbc.m311389200
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Phosphorylation and Chronic Agonist Treatment Atypically Modulate GABAB Receptor Cell Surface Stability

Abstract: GABA B receptors are heterodimeric G protein-coupled receptors that mediate slow synaptic inhibition in the central nervous system. The dynamic control of the cell surface stability of GABA B receptors is likely to be of fundamental importance in the modulation of receptor signaling. Presently, however, this process is poorly understood. Here we demonstrate that GABA B receptors are remarkably stable at the plasma membrane showing little basal endocytosis in cultured cortical and hippocampal neurons. In additi… Show more

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Cited by 104 publications
(116 citation statements)
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“…This finding is in line with so far published data obtained under similar experimental conditions irrespective whether receptors were expressed in neurons (Fairfax et al, 2004;Vargas et al, 2008) or in heterologous expression systems (Fairfax et al, 2004;Grampp et al, 2007;Mutneja et al, 2005;Perroy et al, 2003). These experiments suggest that chronic activation does not promote endocytosis of GABA B receptors.…”
Section: Evidence For Agonist-induced Internalization Of Gaba B Recepsupporting
confidence: 92%
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“…This finding is in line with so far published data obtained under similar experimental conditions irrespective whether receptors were expressed in neurons (Fairfax et al, 2004;Vargas et al, 2008) or in heterologous expression systems (Fairfax et al, 2004;Grampp et al, 2007;Mutneja et al, 2005;Perroy et al, 2003). These experiments suggest that chronic activation does not promote endocytosis of GABA B receptors.…”
Section: Evidence For Agonist-induced Internalization Of Gaba B Recepsupporting
confidence: 92%
“…It was speculated that GABA B receptors might be degraded by non-lysosomal mechanisms since inhibition of lysosomal proteases with leupeptin had no effect on degradation of the receptors (Fairfax et al, 2004). On the other hand, colocalization of GABA B receptors with lysosomes as shown in the supraoptic nucleus, argues for a degradation by the classical pathway via lysosomes (Richards et al, 2005).…”
Section: Introductionmentioning
confidence: 99%
“…Cultures of cortical and hippocampal neurons were prepared as described (8,(17)(18)(19)(20). Nucleofection of cortical and hippocampal neurons (19) was carried out following the manufacturer's protocol (Amaxa, Gaithersburg, MD).…”
Section: Methodsmentioning
confidence: 99%
“…Biotinylation assays to study GABA A R endocytosis, recycling, and degradation were carried out on cultured cortical neurons [5-8 days in vitro (DIV)] as described (20,21) by using 1 mg͞ml sulfo-NHS-biotin (Pierce) at 4°C. Protein levels were then measured by immunoblotting using [ 125 I]-antirabbit polyclonal antibody quantitated with PhosphorImager spectrometry.…”
Section: Methodsmentioning
confidence: 99%
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