Stress-induced non-vesicular extracellular release of complex of Ca^<2+>-binding proteins

胸腺素α原（ProT_α）是一种缺乏信号肽序列的核蛋白，在缺血应激时由神经元和星形胶质细胞释放，通过抗坏死机制发挥独特的神经保护作用。缺血应激诱导的ProT_α释放是由ATP丢失引起的核释放开始的，然后以非囊泡方式释放到细胞外。S100 A13是一种Ca^<2+>结合蛋白，是与ProT_α共释放的主要蛋白。发现ProT_α和S100 A13之间的Ca^<2+>依赖性相互作用需要两种蛋白质的C端肽序列。在凋亡条件下，ProT_α被casase-3切割，产生一个C端缺失肽段，该肽段缺乏核定位信号。而细胞外无ProT_α的释放。这些结果表明，诱导坏死的应激可诱导ProT_α以非囊泡的方式释放到细胞外，而诱导凋亡的应激则不能诱导ProT_α以非囊泡的方式释放到细胞外，这是由于ProT_α失去了与细胞外释放的货物分子S100 A13的相互作用。

The nuclear protein prothymosin-α (ProT_α), which lacks a signal peptide sequence, is release from neurons and astrocytes on ischemic stress and exerts a unique form of neuroprotection through an anti-necrotic mechanism. Ischemic stress-induced ProT_α release is initiated by a nuclear release due to ATP loss, followed by extracellular release in a non-vesicular manner. S100A13, a Ca^<2+>-biniding protein, was identified to be a major protein co-released with ProT_α. The Ca^<2+>-dependent inteaction between ProT_α and S100A13 was found to require the C-terminal peptide sequences of both proteins. Under apoptotic condition, ProT_α was cleaved by casase-3 to generate a C-terminal peptide-deficient fragment, which lacks the nuclear localization signal. However, there was no extracellular release of ProT_α. These results suggest that necrosis-inducing stress induces an extracellula release of ProT_α in a non-vesicular maner, whereas apoptosis-inducing stress does not, owing to the loss of its interaction with S100A13, a cargo molecule for extracellular release.