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Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation

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  3. Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation
Author(s)
Abstract
Sonic hedgehog (Shh) attracts spinal cord commissural axons toward the floorplate. How Shh elicits changes in the growth cone cytoskeleton that drive growth cone turning is unknown. We find that the turning of rat commissural axons up a Shh gradient requires protein synthesis. In particular, Shh stimulation increases beta-actin protein at the growth cone even when the cell bodies have been removed. Therefore, Shh induces the local translation of beta-actin at the growth cone. We hypothesized that this requires zipcode binding protein 1 (ZBP1), an mRNA-binding protein that transports beta-actin mRNA and releases it for local translation upon phosphorylation. We found that Shh stimulation increases phospho-ZBP1 levels in the growth cone. Disruption of ZBP1 phosphorylation in vitro abolished the turning of commissural axons toward a Shh gradient. Disruption of ZBP1 function in vivo in mouse and chick resulted in commissural axon guidance errors. Therefore, ZBP1 is required for Shh to guide commissural axons. This identifies ZBP1 as a new mediator of noncanonical Shh signaling in axon guidance.
Format
Article
Identifier(s)
10.1523/JNEUROSCI.3016-16.2016
Publication Date
2017-02-15
Publication Title
Journal of Neuroscience
Publisher
Society for Neuroscience
Volume
37
Issue
7
First Page
1685
Last Page
1695
Keywords
Subject
Rights
http://rightsstatements.org/vocab/InC/1.0/
License
Creative Commons Attribution 4.0
Community
Healthy Communities Research Institute
Permalinkhttps://oaks.kent.edu/hcri/sonic-hedgehog-guides-axons-zipcode-binding-protein-1-mediated-local-translation
Accessibility
Lepelletier, L., Langlois, S., Kent, C., Welshhans, K., Morin, S., Bassell, G., Yam, P., & Charron, F. (2017). Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation. Journal of Neuroscience. https://doi.org/10.1523/JNEUROSCI.3016-16.2016
Lepelletier, L., S. Langlois, C. Kent, K. Welshhans, S. Morin, G. Bassell, P. Yam, and F. Charron. 2017. Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation. Journal of Neuroscience. https://oaks.kent.edu/node/18534.
Lepelletier, Léa, et al. Sonic Hedgehog Guides Axons via Zipcode Binding Protein 1-Mediated Local Translation. Journal of Neuroscience, 15 Feb. 2017, https://doi.org/10.1523/JNEUROSCI.3016-16.2016.