CNP/cGMP signaling regulates axon branching and growth by modulating microtubule polymerization |
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| Authors: | Caihong Xia Minh Nguyen Amy K Garrison Zhen Zhao Zheng Wang Calum Sutherland Le Ma |
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| Institution: | 1. Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, , Los Angeles, California, 90089;2. Program in Genetic, Molecular and Cellular Biology, Keck School of Medicine, University of Southern California, , Los Angeles, California, 90089;3. Neuroscience Graduate Program, University of Southern California, , Los Angeles, California, 90089;4. Biomedical Research Institute, University of Dundee, Ninewells Medical School, , Dundee, United Kindom;5. Department of Cell and Neurobiology, Keck School of Medicine, , Los Angeles, California, 90089 |
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| Abstract: | 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. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 673–687, 2013 |
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| Keywords: | axon branching and growth microtubule dynamics CNP/cGMP DRG axons CRMP2 |
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