Biologie Cellulaire de la Synapse, IBENS, Ecole Normale Supérieure, Inserm U1024, CNRS UMR8197, Paris, France.
Nat Neurosci. 2010 Nov;13(11):1388-95. doi: 10.1038/nn.2645. Epub 2010 Oct 10.
The regulation of glycine receptor (GlyR) number at synapses is necessary for the efficacy of inhibition and the control of neuronal excitability in the spinal cord. GlyR accumulation at synapses depends on the scaffolding molecule gephyrin and is linked to GlyR synaptic dwell time. However, the mechanisms that tune GlyR synaptic exchanges in response to different neuronal environments are unknown. Integrins are cell adhesion molecules and signaling receptors. Using single quantum dot imaging and fluorescence recovery after photobleaching, we found in rats that β1 and β3 integrins adjust synaptic strength by regulating the synaptic dwell time of both GlyRs and gephyrin. β1 and β3 integrins crosstalked via calcium/calmodulin-dependent protein kinase II and adapted GlyR lateral diffusion and gephyrin-dependent trapping at synapses. This provides a mechanism for maintaining or adjusting the steady state of postsynaptic molecule exchanges and the level of glycinergic inhibition in response to neuron- and glia-derived signals or extracellular matrix remodeling.
甘氨酸受体（GlyR）数量在突触处的调节对于脊髓中抑制作用的效力和神经元兴奋性的控制是必要的。GlyR 在突触处的积累依赖于支架分子神经胶质纤维酸性蛋白（gephyrin），并与 GlyR 突触停留时间相关。然而，调节 GlyR 突触交换以响应不同神经元环境的机制尚不清楚。整合素是细胞黏附分子和信号受体。使用单量子点成像和光漂白后荧光恢复，我们在大鼠中发现β1 和 β3 整合素通过调节 GlyR 和神经胶质纤维酸性蛋白（gephyrin）的突触停留时间来调节突触强度。β1 和 β3 整合素通过钙/钙调蛋白依赖性蛋白激酶 II 相互作用，并适应 GlyR 侧向扩散和 gephyrin 依赖性在突触处的捕获。这为维持或调整突触后分子交换的稳态以及甘氨酸抑制水平提供了一种机制，以响应神经元和神经胶质衍生的信号或细胞外基质重塑。
