Physiological release of endogenous tau is stimulated by neuronal activity.

Physiological release of endogenous tau is stimulated by neuronal activity.
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DOI:
10.1038/embor.2013.15
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发表时间:
2013-04
期刊:
影响因子:
7.7
通讯作者:
Hanger, Diane P.
Hanger, Diane P.
中科院分区:
生物学2区
文献类型:
--
作者:
Pooler, Amy M.;Phillips, Emma C.;Lau, Dawn H. W.;Noble, Wendy;Hanger, Diane P.

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tau病理学的传播与进行性神经变性有关,但tau跨突触传播的机制尚不清楚。我们发现,刺激神经元活动,或AMPA受体激活,诱导tau蛋白从健康,成熟的皮层神经元释放。值得注意的是,与细胞内tau相比,细胞外tau的磷酸化似乎减少。我们还发现AMPA诱导的tau蛋白释放是钙依赖性的。破伤风毒素阻断突触前囊泡释放和河豚毒素抑制神经元活性均显著损害AMPA介导的tau释放。因此,Tau分泌是一个可调节的过程,其失调可能导致疾病中Tau病理学的传播。
Propagation of tau pathology is linked with progressive neurodegeneration, but the mechanism underlying trans-synaptic spread of tau is unknown. We show that stimulation of neuronal activity, or AMPA receptor activation, induces tau release from healthy, mature cortical neurons. Notably, phosphorylation of extracellular tau appears reduced in comparison with intracellular tau. We also find that AMPA-induced release of tau is calcium-dependent. Blocking pre-synaptic vesicle release by tetanus toxin and inhibiting neuronal activity with tetrodotoxin both significantly impair AMPA-mediated tau release. Tau secretion is therefore a regulatable process, dysregulation of which could lead to the spread of tau pathology in disease.
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