Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity
Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity
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DOI：
10.1002/neu.1046
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发表时间：
2001-08-01
期刊：
影响因子：
--
通讯作者：
Higgins, D
中科院分区：
文献类型：
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作者：
Guo, X;Lin, Y;Higgins, D
骨形态发生蛋白（BMPs）诱导培养的交感神经元树突生长，然而，介导这种树突促进活动的信号通路尚未被以前的特点。在这里，我们报告的信号事件，调节这些传入过程的增长的研究。我们发现Smad 1在交感神经元中表达，BMP快速诱导其磷酸化并从细胞质易位到细胞核。此外，一个显性负性形式的Smad 1抑制BMP-7诱导的树突状细胞的生长，这表明在BMP-7的这种生物活性的要求富尔Smad 1激活。Smad 1和蛋白酶体介导的降解系统中所涉及的组件之间的物理相互作用与酵母双杂交筛选检测，从而促使检查蛋白酶体抑制剂对树突状细胞生长的影响。Lactacystin和ALLN（N-乙酰基-Leu-Leunorleucinal）选择性阻断BMP-7诱导的树突状细胞生长，而不会对细胞活力或轴突生长产生不利影响。此外，对转染的P19细胞的研究表明，蛋白酶体抑制剂直接阻断Smad 1对Tlx-2启动子转录活性的影响。这些数据表明，BMP诱导的树枝状细胞生长需要Smad 1激活，并涉及蛋白酶体介导的降解事件。(C)2001年John Wiley & Sons。Inc.
Bone morphogenetic proteins (BMPs) induce dendritic growth in cultured sympathetic neurons; however, the signaling pathways that mediate this dendrite-promoting activity have not been previously characterized. Here we report studies of the signaling events that regulate the growth of these afferent processes. We find that Smad1 is expressed in sympathetic neurons and that BMPs rapidly induce its phosphorylation and translocation from the cytoplasm to the nucleus. Furthermore, a dominant negative form of Smad 1 inhibits BMP-7-induced dendritic growth, suggesting a requirement fur Smad1 activation in this biological activity of BMP-7. A physical interaction between Smad1 and components involved in the proteasome-mediated degradation system was detected with a yeast two-hybrid screen, thereby prompting an examination of the effects of proteasome inhibitors on dendritic growth. Lactacystin and ALLN (N-acetyl-Leu-Leunorleucinal) selectively blocked BMP-7-induced dendritic growth without adversely affecting either cell viability or axonal growth. Moreover, studies of transfected P19 cells suggest that the proteasome inhibitors directly block the effects of Smad1 on the transcriptional activity of the Tlx-2 promoter. These data indicate that BMP-induced dendritic growth requires Smad1 activation and involves proteasome-mediated degradation events. (C) 2001 John Wiley & Sons. Inc.