Function of an axonal chemoattractant modulated by metalloprotease activity
Function of an axonal chemoattractant modulated by metalloprotease activity
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DOI：
10.1126/science.289.5483.1365
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发表时间：
2000-08-25
期刊：
影响因子：
56.9
通讯作者：
Tessier-Lavigne, M
中科院分区：
文献类型：
--
作者：
Galko, MJ;Tessier-Lavigne, M
轴突化学引诱物netrin-1通过激活其受体DCC（结直肠癌中的DCC）来引导脊髓连合轴突。我们已经发现金属蛋白酶的化学抑制剂在体外增强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，并且抑制剂阻断DCC的蛋白水解加工并引起脊髓外植体内轴突上DCC蛋白水平的增加。因此，抑制剂增强netrin活性可能是由于轴突上DCC的稳定化，蛋白水解活性可以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。
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.