title: CNP/cGMP signaling regulates axon branching and growth by modulating microtubule polymerization.
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.
authors: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors: Caihong
authors: C
authors: Xia
authors: Minh
authors: M
authors: Nguyen
authors: Amy K
authors: AK
authors: Garrison
authors: Zhen
authors: Z
authors: Zhao
authors: Zheng
authors: Z
authors: Wang
authors: Calum
authors: C
authors: Sutherland
authors: Le
authors: L
authors: Ma
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008870:Microtubules / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D050257:Tubulin Modulators; C095114:collapsin response mediator protein-2; D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP; D015739:Nocodazole
keywords: CNP/cGMP; CRMP2; DRG axons; axon branching and growth; microtubule dynamics