title: Regulation of glycine receptor diffusion properties and gephyrin interactions by protein kinase C.
abstract: Glycine receptors (GlyRs) can dynamically exchange between synaptic and extrasynaptic locations through lateral diffusion within the plasma membrane. Their accumulation at inhibitory synapses depends on the interaction of the β-subunit of the GlyR with the synaptic scaffold protein gephyrin. An alteration of receptor-gephyrin binding could thus shift the equilibrium between synaptic and extrasynaptic GlyRs and modulate the strength of inhibitory neurotransmission. Using a combination of dynamic imaging and biochemical approaches, we have characterised the molecular mechanism that links the GlyR-gephyrin interaction with GlyR diffusion and synaptic localisation. We have identified a protein kinase C (PKC) phosphorylation site within the cytoplasmic domain of the β-subunit of the GlyR (residue S403) that causes a reduction of the binding affinity between the receptor and gephyrin. In consequence, the receptor's diffusion in the plasma membrane is accelerated and GlyRs accumulate less strongly at synapses. We propose that the regulation of GlyR dynamics by PKC thus contributes to the plasticity of inhibitory synapses and may be involved in maladaptive forms of synaptic plasticity.
authors.affiliation: Biologie Cellulaire de la Synapse, Institut de Biologie de l'École Normale Supérieure, Inserm U, Paris, France.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Specht
authors.forename: Nora
authors.initials: N
authors.lastname: Grünewald
authors.forename: Olivier
authors.initials: O
authors.lastname: Pascual
authors.forename: Nina
authors.initials: N
authors.lastname: Rostgaard
authors.forename: Günter
authors.initials: G
authors.lastname: Schwarz
authors.forename: Antoine
authors.initials: A
authors.lastname: Triller
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D018009:Receptors, Glycine; C073441:gephyrin; D011493:Protein Kinase C