Biologie Cellulaire de la Synapse, Institut de Biologie de l'École Normale Supérieure, Inserm U, Paris, France.
EMBO J. 2011 Aug 9;30(18):3842-53. doi: 10.1038/emboj.2011.276.
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.
甘氨酸受体 (GlyRs) 可以通过质膜内的侧向扩散在突触和 extrasynaptic 位置之间动态交换。它们在抑制性突触处的积累取决于 GlyR 的 β 亚基与突触支架蛋白 gephyrin 的相互作用。因此，受体-gerphyrin 结合的改变可以改变突触和 extrasynaptic GlyRs 之间的平衡，调节抑制性神经传递的强度。我们使用动态成像和生化方法的组合，描述了将 GlyR-gephyrin 相互作用与 GlyR 扩散和突触定位联系起来的分子机制。我们已经确定了 GlyR 的 β 亚基细胞质结构域内的蛋白激酶 C (PKC) 磷酸化位点（残基 S403），该位点导致受体与 gephyrin 之间的结合亲和力降低。结果，受体在质膜中的扩散加速，GlyRs 在突触处的积累较弱。我们提出，PKC 对 GlyR 动力学的调节有助于抑制性突触的可塑性，并且可能参与突触可塑性的适应不良形式。
