Galko M J, Tessier-Lavigne M
Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Science. 2000 Aug 25;289(5483):1365-7. doi: 10.1126/science.289.5483.1365.
The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. We have also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors.
轴突化学引诱剂netrin-1通过激活其受体DCC（结直肠癌缺失基因）来引导脊髓连合轴突。我们发现金属蛋白酶的化学抑制剂在体外可增强netrin介导的轴突生长。我们还发现DCC是金属蛋白酶依赖性胞外域脱落的底物，并且这些抑制剂可阻断DCC的蛋白水解加工，并导致脊髓外植体轴突上DCC蛋白水平升高。因此，抑制剂对netrin活性的增强作用可能是由于轴突上DCC的稳定，而蛋白水解活性可能通过控制功能性细胞外轴突导向受体的数量来调节轴突迁移。
