The regulatory mechanisms and the physiological significance of SNAP-25 phosphorylation in mouse brain.

SNAP-25在通过胞吐作用释放神经递质中起关键作用。蛋白激酶C使SNAP-25在Ser 187处磷酸化，然而这种磷酸化事件在脑功能中的生理意义仍不清楚。我们发现SNAP-25磷酸化在冷水束缚应激后小鼠大脑中迅速增加。SNAP-25的基础和应激诱导的磷酸化在应激相关的脑区都很高，并且磷酸化的程度随着应激量的增加而增加。静脉注射肾上腺素增加SNAP-25磷酸化，尽管在肾上腺切除小鼠中仍然观察到应激诱导的磷酸化。这些结果表明，SNAP-25磷酸化是通过中枢和外周机制以应激依赖性方式调节的。我们还研究了SNAP-25的去磷酸化，发现蛋白磷酸酶2A通过Ca 2+依赖性和非依赖性机制参与SNAP-25的去磷酸化。

SNAP-25 plays a crucial role in neurotransmitter release by exocytosis. Protein kinase C phosphorylates SNAP-25 at Ser187, however the physiological significance of this phosphorylation event in brain function remains unclear. We found that SNAP-25 phosphorylation increased rapidly in the mouse brain following cold-water restraint stress. Both basal and stress-induced phosphorylation of SNAP-25 were high in stress-related brain regions and the extent of phosphorylation increased with increasing amounts of stress. Intravenous administration of adrenaline increased SNAP-25 phosphorylation, although stress-induced phosphorylation was still observed in adrenalectomized mice. These results indicate that SNAP-25 phosphorylation is regulated in a stress-dependent manner through both central and peripheral mechanisms. We also investigated SNAP-25 dephosphorylation, and found that protein phosphatase 2A participates in SNAP-25 dephosphorylation through Ca2+-dependent and independent mechanisms.