Determination of cell adhesion sites of neuropilin-1.

Determination of cell adhesion sites of neuropilin-1.
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DOI:
10.1083/jcb.148.6.1283
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发表时间:
2000-03-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Fujisawa H
Fujisawa H
中科院分区:
其他
文献类型:
--
作者:
Shimizu M;Murakami Y;Suto F;Fujisawa H

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Neuropilin-1是一种1型膜蛋白,具有三种不同的功能。首先,它可以通过异嗜性分子相互作用介导细胞粘附。第二,在神经元细胞中,neuropilin-1结合3类semaphorins,这是神经元的化学排斥,并在轴突的定向引导中发挥作用。神经纤毛蛋白-1与丛蛋白A亚家族成员形成复合物,并介导脑信号蛋白引起的抑制信号进入神经元。第三,在内皮细胞中,神经纤毛蛋白-1结合有效的内皮细胞有丝分裂原,血管内皮生长因子(VEGF)165,并调节血管形成。虽然已经分析了神经纤毛蛋白-1中3类信号蛋白和VEGF 165的结合位点,但尚未鉴定出该分子的细胞粘附活性所涉及的位点。在这项研究中,我们产生了各种突变的neuropilin-1,并测试其细胞粘附活性。我们发现,b1和b2结构域内的神经纤毛蛋白-1的细胞外部分所需的细胞粘附活性,并在b1和b2结构域的18个氨基酸的延伸肽足以诱导细胞粘附活性。此外,我们证明了神经纤毛蛋白-1的细胞粘附配体是蛋白质,分布在胚胎间充质细胞中,但不同于3类脑信号蛋白,VEGF或丛蛋白。
Neuropilin-1 is a type 1 membrane protein with three distinct functions. First, it can mediate cell adhesion via a heterophilic molecular interaction. Second, in neuronal cells, neuropilin-1 binds the class 3 semaphorins, which are neuronal chemorepellents, and plays a role in the directional guidance of axons. Neuropilin-1 is expected to form complexes with the plexinA subfamily members and mediate the semaphorin-elicited inhibitory signals into neurons. Third, in endothelial cells, neuropilin-1 binds a potent endothelial cell mitogen, vascular endothelial growth factor (VEGF)165, and regulates vessel formation. Though the binding sites in neuropilin-1 for the class 3 semaphorins and VEGF165 have been analyzed, the sites involved in cell adhesion activity of the molecule have not been identified. In this study, we produced a variety of mutant neuropilin-1s and tested their cell adhesion activity. We showed that the b1 and b2 domains within the extracellular segment of neuropilin-1 were required for the cell adhesion activity, and peptides with an 18–amino acid stretch in the b1 and b2 domains were sufficient to induce the cell adhesion activity. In addition, we demonstrated that the cell adhesion ligands for neuropilin-1 were proteins and distributed in embryonic mesenchymal cells but distinct from the class 3 semaphorins, VEGF, or plexins.
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