Caspase activation via Dependence Receptors in the absence of ligand

In the presence of Netrin1, DCC and UNC5 generate attractive and repulsive signals to growing axons. In the absence of Netrin-1, DCC induces cell death signaling initiated via caspase cleavage of DCC and the interaction of caspase-9. Recent reports have shown that UNC5 receptors similarly induce apoptosis in the absence of Netrin-1. These reactions proceed without a requirement for cytochrome c release from mitochondria or interaction with apoptotic protease activating factor 1 (APAF1). DCC thus regulates an apoptosome-independent pathway for caspase activation. DCC and UNC-5 are hence defined as dependence receptors. Dependence receptors exhibit dual functions depending on the availability of ligand. They create cellular states of dependence on their respective ligands by either inducing apoptosis when unoccupied by the ligand, or inhibiting apoptosis in the presence of the ligand.

在Netrin1的存在下，DCC和UNC5向生长的轴突产生吸引和排斥信号。Netrin-1缺乏时，DCC诱导细胞死亡信号，该信号通过caspase对DCC的剪切以及caspase-9的相互作用启动。近期的研究报告显示，UNC5受体在Netrin-1缺乏的情况下亦能诱导细胞凋亡。这些反应的发生无需线粒体释放细胞色素c或与凋亡蛋白酶激活因子1（APAF1）的相互作用。因此，DCC调控了不依赖凋亡体（apoptosome）的caspase激活途径。DCC和UNC-5因此被定义为依赖性受体。依赖性受体根据配体的存在与否展现出双重功能：当配体未结合时，通过诱导细胞凋亡来形成对相应配体的依赖性细胞状态；而当配体存在时，则抑制细胞凋亡。