VEGF189 binds NRP1 and is sufficient for VEGF/NRP1-dependent neuronal patterning in the developing brain.

VEGF189 binds NRP1 and is sufficient for VEGF/NRP1-dependent neuronal patterning in the developing brain.
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DOI:
10.1242/dev.115998
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发表时间:
2015-01-15
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Ruhrberg C
Ruhrberg C
中科院分区:
其他
文献类型:
--
作者:
Tillo M;Erskine L;Cariboni A;Fantin A;Joyce A;Denti L;Ruhrberg C

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血管内皮生长因子(VEGFA, VEGF)调节神经血管模式。Vegfa基因的选择性剪接产生三种主要亚型,分别为VEGF121、VEGF165和VEGF189。VEGF165结合跨膜蛋白neuropilin 1 (NRP1),促进神经元亚群的迁移、存活和轴突引导,而VEGF121不能激活NRP1依赖的神经元反应。相比之下,VEGF189在nrp1介导的信号通路中的作用尚未被研究。在这里,我们将表达研究和原位配体结合实验与转基因小鼠和体外模型的分析结合起来,证明VEGF189可以结合NRP1并促进NRP1依赖的神经元反应。摘要:虽然VEGF165被认为是唯一的通过神经匹素1 (NRP1)作用的VEGF亚型,但VEGF189在几种发育中的小鼠神经元中也结合并通过NRP1发出信号。
The vascular endothelial growth factor (VEGFA, VEGF) regulates neurovascular patterning. Alternative splicing of the Vegfa gene gives rise to three major isoforms termed VEGF121, VEGF165 and VEGF189. VEGF165 binds the transmembrane protein neuropilin 1 (NRP1) and promotes the migration, survival and axon guidance of subsets of neurons, whereas VEGF121 cannot activate NRP1-dependent neuronal responses. By contrast, the role of VEGF189 in NRP1-mediated signalling pathways has not yet been examined. Here, we have combined expression studies and in situ ligand-binding assays with the analysis of genetically altered mice and in vitro models to demonstrate that VEGF189 can bind NRP1 and promote NRP1-dependent neuronal responses. Summary: Although VEGF165 was thought to be the sole VEGF isoform acting through neuropilin 1 (NRP1), VEGF189 also binds to and signals through NRP1 in several types of developing mouse neurons.
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