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Identification of serine 867 as new phosphorylation site on the GABA(B) receptor : characterization of physiological effects

Abdel Aziz, Said. Identification of serine 867 as new phosphorylation site on the GABA(B) receptor : characterization of physiological effects. 2011, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_9476

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Abstract

The GABAB receptor is the metabotropic receptor for γ-aminobutyric acid (GABA), the main inhibitory
neurotransmitter in the mammalian central nervous system (CNS). The functional receptor is a
heteromer consisting of a GABAB1 and GABAB2 subunit. Two isoforms from the GABAB1 subunit exist;
the GABAB1a and the GABAB1b isoform, whose distribution pattern differs throughout the brain. GABAB
receptors manifest their inhibitory action by influencing adenylate cyclase activity, presynaptic
voltage sensitive Ca2+ channels and postsynaptic rectifying K+ channels. The large variety of
neurological and psychiatric disorders e.g. addiction, epilepsy, nociception and depression caused by
GABAB receptors dysfunctions, highlight the importance for GABAB regulatory mechanisms. One such
regulatory mechanism is phosphorylation which is the principal way to regulate GABAB receptor
functioning. In vivo, two phosphorylation sites on GABAB receptors were identified; serine 892 and
serine 783 and both sites play a role in synaptic plasticity. Phosphorylation of serine 892 prolongs
the inhibitory impact of GABAB receptors activity on the CNS and serine 783 is ascribed for its
neuroprotective benefits.
The aim of this thesis was to study the modulatory effect of phosphorylation on GABAB receptor
functioning. The identification of serine 867, a novel physiological relevant phosphorylation site on
GABAB receptors, contrasts with the previous serine sites. Indeed, the serine 867 is positioned on the
GABAB1 subunit, constrasting with the GABAB2 localisation of the serines 892 and 783. Interestingly,
serine 867 phosphorylation is mediated by CaMKII, an abundant and relevant kinase in the CNS.
Consequently, it is proposed that serine 867 phosphorylation could regulate surface availability of
GABAB receptors under neuronal activation leading to synaptic plasticity modulation.
Advisors:Bettler, Bernhard
Committee Members:Rüegg, Markus A.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
Item Type:Thesis
Thesis no:9476
Bibsysno:Link to catalogue
Number of Pages:93 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:10 Jun 2011 08:13

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