Nakamura F, Tanaka M, Takahashi T, Kalb R G, Strittmatter S M
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Neuron. 1998 Nov;21(5):1093-100. doi: 10.1016/s0896-6273(00)80626-1.
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.
当可溶性信号素D（semD）与生长锥神经纤毛蛋白-1（Npn-1）结合时，体感轴突的生长受到排斥。在此，对Npn-1突变体的semD配体结合研究表明，信号素结构域与Npn-1的氨基末端四分之一或补体结合（CUB）结构域结合。通过单纯疱疹病毒（HSV）介导在鸡视网膜神经节细胞中表达Npn-1突变体，我们发现semD诱导的生长锥塌陷需要Npn-1胞外域的两个片段，即CUB结构域和近膜部分或MAM（meprin、A5、μ）结构域。相比之下，Npn-1的跨膜段和胞质尾对于生物活性并非必需。这些数据表明，Npn-1的CUB和MAM胞外域与另一种跨膜生长锥蛋白相互作用，进而将semD信号转化为轴突排斥。
