PDF(Sci-hub)
Abstract：
Auxiliary α2δ subunits are important proteins for trafficking of voltage-gated calcium channels (CaV) at the active zones of synapses. We have previously shown that the post-translational proteolytic cleavage of α2δ is essential for their modulatory effects on the trafficking of N-type (CaV2.2) calcium channels (Kadurin et al., 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α2δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α2δ is restored. We also show that asynchronous release is influenced by the maturation of α2δ-1, highlighting the role of CaV channels in this component of vesicular release. We present additional evidence that CaV2.2 co-immunoprecipitates preferentially with cleaved wild-type α2δ. Our data indicate that the proteolytic maturation increases the association of α2δ-1 with CaV channel complex and is essential for its function on synaptic release.
摘要：
辅助α2δ亚基是在突触活性区运输电压门控钙通道（CaV）的重要蛋白质。我们先前已经表明，α2δ的翻译后蛋白水解裂解对于它们对N型（CaV2.2）钙通道运输的调节作用至关重要（Kadurin等人。,2016)。我们通过显示当大鼠神经元中表达未切割的α2δ时，突触前囊泡释放的可能性降低，并且当恢复α2δ的裂解时，这种抑制作用被逆转，从而在此扩展了这些结果。我们还表明，α2δ-1的成熟会影响异步释放，从而突显了CaV通道在囊泡释放中的作用。我们提供了其他证据，表明CaV2.2优先与切割的野生型α2δ共免疫沉淀。我们的数据表明，蛋白水解成熟增加了α2δ-1与CaV通道复合物的缔合，并且对于其对突触释放的功能至关重要。
