Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites

Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites
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发育中雏鸡的神经元和非神经元 Collapsin-1 结合位点与其他信号蛋白结合位点不同

DOI:
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发表时间:
1997
影响因子:
5.3
通讯作者:
S. Strittmatter
S. Strittmatter
中科院分区:
医学1区
文献类型:
--
作者:
Takuya Takahashi;F. Nakamura;S. Strittmatter

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细胞外蛋白中的塌陷素和信号素家族通过排斥轴突和折叠生长锥体而参与轴突路径的发现。为了探讨崩解素-1的作用机制,我们表达并纯化了一个截短的崩解素-1-碱性磷酸酶融合蛋白(CAP-4)。该蛋白保留了作为DRG生长锥体崩解剂的生物活性,并以低纳摩尔亲和力饱和地与DRG神经元结合。CAP-4特异性结合位点存在于DRG神经元、交感神经元和运动神经元上,而不存在于视网膜、皮质或脑干神经元上。在神经系统外,CAP-4的高水平结合部位存在于主要血管周围的间质、发育中的骨和肺中。这些位点为SEMA III(−/−)小鼠中受扰的非神经元组织依赖崩塌蛋白-1的模式提供了底物。小鼠信号素D/III和鸡崩溃蛋白-1融合蛋白的染色模式彼此难以区分,但与信号素B和M-信号素F融合蛋白的染色模式完全不同。这些数据表明,存在一类在复杂性上类似于信号素配体家族的高亲和力信号素结合位点。
The collapsin and semaphorin family of extracellular proteins contributes to axonal path finding by repulsing axons and collapsing growth cones. To explore the mechanism of collapsin-1 action, we expressed and purified a truncated collapsin-1–alkaline phosphatase fusion protein (CAP-4). This protein retains biological activity as a DRG growth cone collapsing agent and saturably binds to DRG neurons with low nanomolar affinity. Specific CAP-4 binding sites are present on DRG neurons, sympathetic neurons, and motoneurons, but not on retinal, cortical, or brainstem neurons. Outside the nervous system, high levels of CAP-4 binding sites are present in the mesenchyme surrounding major blood vessels and developing bone and in lung. These sites provide a substrate for the collapsin-1-dependent patterning of non-neuronal tissues perturbed in sema III (−/−) mice. The staining patterns for mouse semaphorin D/III and chick collapsin-1 fusion proteins are indistinguishable from one another but quite separate from that for semaphorin B and M-semaphorin F fusion proteins. These data imply that a family of high-affinity semaphorin binding sites similar in complexity to the semaphorin ligand family exists.
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