Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor
Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor
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DOI：
10.1523/jneurosci.21-10-03332.2001
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发表时间：
2001-05-15
影响因子：
5.3
通讯作者：
Thomasset, N
中科院分区：
文献类型：
--
作者：
Bagnard, D;Vaillant, C;Thomasset, N
细胞与微环境之间的动态和协调的相互作用控制着细胞的迁移、增殖和凋亡，由不同的细胞表面分子介导。我们研究了神经外胚层祖细胞系Dev对一个引导分子信号蛋白3A （Sema3A）的反应，Sema3A之前被描述为轴突的一个排斥崩溃信号，我们已经证明Sema3A作为一个排斥引导提示，用于迁移祖细胞，并且在长期应用中诱导凋亡。排斥和诱导细胞死亡都是由Sema3A受体的配体结合成分neuropilin-1介导的。血管内皮生长因子VEGF165可拮抗sema3a诱导的细胞凋亡，促进细胞存活、迁移和增殖。令人惊讶的是，Sema3A的排斥也依赖于VEGFR1的表达，VEGFR1是一种VEGF165受体，在Dev细胞中表达。此外，我们发现Sema3A的这些排斥作用需要酪氨酸激酶活性，而酪氨酸激酶活性可归因于VEGFR1。这些结果表明，引导分子和血管生成因子之间的平衡可以通过共享受体调节神经祖细胞的迁移、凋亡（或存活）和增殖。
The dynamic and coordinated interaction between cells and their microenvironment controls cell migration, proliferation, and apoptosis, mediated by different cell surface molecules. We have studied the response of a neuroectodermal progenitor cell line, Dev, to a guidance molecule, semaphorin 3A (Sema3A), described previously as a repellent-collapsing signal for axons, and we have shown that Sema3A acts as a repellent guidance cue for migrating progenitor cells and, on prolonged application, induces apoptosis. Both repulsion and induction of cell death are mediated by neuropilin-1, the ligand-binding component of the Sema3A receptor. The vascular endothelial growth factor, VEGF165, antagonizes Sema3A-induced apoptosis and promotes cell survival, migration, and proliferation. Surprisingly, repulsion by Sema3A also depends on expression of VEGFR1, a VEGF165 receptor, expressed in Dev cells. Moreover, we found that these repulsive effects of Sema3A require tyrosine kinase activity, which can be attributed to VEGFR1. These results indicate that the balance between guidance molecules and angiogenic factors can modulate the migration, apoptosis (or survival), and proliferation of neural progenitor cells through shared receptors.