Linked Life Data

20655480

Source:http://linkedlifedata.com/resource/pubmed/id/20655480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-7-26
pubmed:abstractText
GABA(B) receptors (GABA(B)R) are heterodimeric G protein-coupled receptors (GPCRs) that mediate slow and prolonged inhibitory signals in the central nervous system. The signaling of GPCRs is under stringent control and is subject to regulation by multiple posttranslational mechanisms. The beta-adrenergic receptor is a prototypic GPCR. Like most GPCRs, prolonged exposure of this receptor to agonist induces phosphorylation of multiple intracellular residues that is largely dependent upon the activity of G protein-coupled receptor kinases (GRKs). Phosphorylation terminates receptor-effector coupling and promotes both interaction with beta-arrestins and removal from the plasma membrane via clathrin-dependent endocytosis. Emerging evidence for GABA(B)Rs suggests that these GPCRs do not conform to this mode of regulation. Studies using both native and recombinant receptor preparations have demonstrated that GABA(B)Rs do not undergo agonist-induced internalization and are not GRK substrates. Moreover, whilst GABA(B)Rs undergo clathrin-dependent constitutive endocytosis, it is generally accepted that their rates of internalization are not modified by prolonged agonist exposure. Biochemical studies have revealed that GABA(B)Rs are phosphorylated on multiple residues within the cytoplasmic domains of both the R1 and R2 subunits by cAMP-dependent protein kinase and 5'AMP-dependent protein kinase (AMPK). Here we discuss the role that this phosphorylation plays in determining GABA(B)R effector coupling and their trafficking within the endocytic pathway and go on to evaluate the significance of GABA(B)R phosphorylation in controlling neuronal excitability under normal and pathological conditions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1557-8925
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-22
pubmed:dateRevised
2011-3-11
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Functional modulation of GABAB receptors by protein kinases and receptor trafficking.
pubmed:affiliation
Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural