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.
Wu, R, Yao, F, Liu, J, Finley RL, Jr, Morgan, M, Chen, YQ, Thorburn, A
Matsuda, K, Tanikawa, C, Arakawa, H, Fukuda, S, Nakamura, Y
Mehlen, P, Fearon, ER
Pong, RC, Cipriano, SC, Yao, F, Hsieh, JT, Krepulat, F, Chen, YQ, Fang, B
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