Department of Medical Pharmacology and Consiglio Nazionale delle Ricerche (CNR) Institute of Neuroscience, University of Milano, 20129 Milano, Italy.
Cereb Cortex. 2013 Mar;23(3):531-41. doi: 10.1093/cercor/bhs026. Epub 2012 Mar 7.
Activation of protein kinase A (PKA) pathway at presynaptic terminals plays a crucial role in the supply of synaptic vesicles (SVs) from the reserve pool, affecting the steady-state level of activity and the reconstitution of the readily releasable pool after intense stimulation. However, the identity of the stimuli activating this pathway is undefined. Using fluorescence resonance energy transfer and molecular genetic, we show that kainate, through the activation of presynaptic kainate receptors, induces PKA activation and enhances synapsin I phosphorylation at PKA-specific residues. This leads to a dispersion of synapsin I immunoreactivity, which is accompanied by a PKA-dependent increase in the rate of SV recycling at the growth cone and by an enhanced miniature excitatory postsynaptic currents frequency in mature networks. Selective activation of this pathway is induced by the native neurotransmitter glutamate, when applied in the high nanomolar range. These data identify glutamate, specifically acting on KARs, as one of the stimuli able to induce phosphorylation of synapsin at PKA sites, both at the axonal growth cone and at the mature synapse, thus increasing SV availability and contributing to plasticity phenomena.
蛋白激酶 A (PKA) 途径在突触前末梢的激活在从储备池供应突触小泡 (SVs) 中起着至关重要的作用，影响活性的稳态水平和强烈刺激后易释放池的重建。然而，激活该途径的刺激物的身份尚未确定。我们使用荧光共振能量转移和分子遗传学方法表明，海人酸通过激活突触前海人酸受体，诱导 PKA 的激活，并增强 PKA 特异性残基处的突触丝蛋白 I 的磷酸化。这导致突触丝蛋白 I 免疫反应性的分散，伴随着生长锥处 SV 再循环率的 PKA 依赖性增加，以及成熟网络中兴奋性突触后电流频率的增强。当以高纳摩尔范围施加时，这种途径的选择性激活是由内源性神经递质谷氨酸诱导的。这些数据表明，谷氨酸特异性作用于 KARs，是能够诱导突触丝蛋白在 PKA 位点磷酸化的刺激物之一，无论是在轴突生长锥还是在成熟突触中，从而增加 SV 的可用性，并有助于可塑性现象。
