期刊
DEVELOPMENTAL NEUROBIOLOGY
卷 73, 期 9, 页码 673-687出版社
WILEY
DOI: 10.1002/dneu.22078
关键词
axon branching and growth; microtubule dynamics; CNP; cGMP; DRG axons; CRMP2
资金
- Whitehall Foundation
- NIH-NINDS
- Zumberge Research and Innovation Fund of USC
- Alzheimer's Research Trust
- Alzheimers Research UK [ART-PG2007-4, ART-PG2005-1] Funding Source: researchfish
The peptide hormone CNP has recently been found to positively regulate axon branching and growth via activation of cGMP signaling in embryonic dorsal root ganglion (DRG) neurons, but the cellular mechanisms mediating the regulation of these developmental processes have not been established. In this study, we provide evidence linking CNP/cGMP signaling to microtubule dynamics via the microtubule regulator CRMP2. First, phosphorylation of CRMP2 can be suppressed by cGMP activation in embryonic DRG neurons, and non-phosphorylated CRMP2 promotes axon branching and growth. In addition, real time analysis of growing microtubule ends indicates a similar correlation of CRMP2 phosphorylation and its activity in promoting microtubule polymerization rates and durations in both COS cells and DRG neuron growth cones. Moreover, direct activation of cGMP signaling leads to increased assembly of dynamic microtubules in DRG growth cones. Finally, low doses of a microtubule depolymerization drug nocodazole block CNP/cGMP-dependent axon branching and growth. Taken together, our results support a critical role of microtubule dynamics in mediating CNP/cGMP regulation of axonal development. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 673-687, 2013
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据