Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse
Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse
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DOI：
10.1016/s0896-6273(00)80626-1
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发表时间：
1998-11-01
期刊：
影响因子：
16.2
通讯作者：
Strittmatter, SM
中科院分区：
文献类型：
--
作者：
Nakamura, F;Tanaka, M;Strittmatter, SM
当可溶性脑信号蛋白D（semD）与生长锥神经纤毛蛋白-1（Npn-1）结合时，体感轴突生长被排斥。在这里，Npn-1突变体的semD配体结合研究表明，sema结构域结合Npn-1的氨基末端四分之一，或补体结合（CUB）结构域。通过单纯疱疹病毒（HSV-）介导的Npn-1突变体在鸡视网膜神经节细胞中的表达，我们表明semD诱导的生长锥崩溃需要两个部分的胞外域的Npn-1，CUB域和质膜部分，或MAM（meprin，A5，mu）域。相反，Npn-1的跨膜区段和胞质尾区对于生物活性不是必需的。这些数据意味着Npn-1的CUB和MAM胞外域与另一种跨膜生长锥蛋白相互作用，该蛋白反过来将semD信号转导成轴突排斥。
Somatosensory axon outgrowth is repulsed when soluble semaphorin D (semD) binds to growth cone neuropilin-1 (Npn-1). Here, semD ligand binding studies of Npn-1 mutants demonstrate that the sema domain binds to the amino-terminal quarter, or complement-binding (CUB) domain, of Npn-1. By herpes simplex virus- (HSV-) mediated expression of Npn-1 mutants in chick retinal ganglion cells, we show that semD-induced growth cone collapse requires two segments of the ectodomain of Npn-1, the CUB domain and the juxtamembrane portion, or MAM (meprin, A5, mu) domain. In contrast, the transmembrane segment and cytoplasmic tail of Npn-1 are not required for biologic activity. These data imply that the CUB and MAM ectodomains of Npn-1 interact with another transmembrane growth cone protein that in turn transduces a semD signal into axon repulsion.