Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independently of catalytic function
Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independently of catalytic function
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DOI：
10.1242/jcs.135137
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发表时间：
2014-05-15
影响因子：
4
通讯作者：
Boise, Lawrence H.
中科院分区：
文献类型：
--
作者：
Brentnall, Matthew;Weir, David B.;Boise, Lawrence H.
半胱天冬酶-3是在细胞凋亡期间在线粒体外膜透化（MOMP）下游活化的效应半胱天冬酶。然而，先前的工作已经证明，caspase-3缺陷型小鼠胚胎成纤维细胞（MEFs）对神经介导的细胞死亡具有抗性，并显示出线粒体凋亡事件的延迟，包括Bax激活，MOMP和细胞色素c的释放。在这里，我们表明，caspase-3调节纤连蛋白的分泌和影响细胞形态，粘附和迁移。令人惊讶的是，caspase-3的催化活性不是这些非凋亡功能所必需的。此外，我们发现caspase-3缺陷的MEFs对失巢凋亡的死亡没有抵抗力，外源性纤连蛋白保护野生型MEFs免于血清戒断诱导的细胞死亡。总之，我们的数据表明，procaspase-3具有非凋亡功能，它调节纤连蛋白的分泌，影响形态，粘附和迁移。此外，这种新的procaspase-3功能可能会改变细胞的凋亡阈值。
Caspase-3 is an effector caspase that is activated downstream of mitochondrial outer-membrane permeabilization (MOMP) during apoptosis. However, previous work has demonstrated that caspase-3-deficient mouse embryonic fibroblasts (MEFs) are resistant to mitochondrially mediated cell death and display a delay in the mitochondrial events of apoptosis, including Bax activation, MOMP and release of cytochrome c. Here, we show that caspase-3 regulates fibronectin secretion and impacts on cell morphology, adhesion and migration. Surprisingly, the catalytic activity of caspase-3 is not required for these non-apoptotic functions. Moreover, we found that caspase-3-deficient MEFs are not resistant to death by anoikis and that exogenous fibronectin protects wild-type MEFs from cell death induced by serum withdrawal. Taken together, our data indicate that procaspase-3 has a non-apoptotic function; it regulates the secretion of fibronectin and influences morphology, adhesion and migration. Furthermore, this novel procaspase-3 function might alter the apoptotic threshold of the cell.