Department of Neurobiology; Benard Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Developmental Neuroscience | Molecular and Cellular Neuroscience
Netrin is a key axon guidance cue that orients axon growth during neural circuit formation. However, the mechanisms regulating netrin and its receptors in the extracellular milieu are largely unknown. Here we demonstrate that in Caenorhabditis elegans, LON-2/glypican, a heparan sulfate proteoglycan, modulates UNC-6/netrin signaling and may do this through interactions with the UNC-40/DCC receptor. We show that developing axons misorient in the absence of LON-2/glypican when the SLT-1/slit guidance pathway is compromised and that LON-2/glypican functions in both the attractive and repulsive UNC-6/netrin pathways. We find that the core LON-2/glypican protein, lacking its heparan sulfate chains, and secreted forms of LON-2/glypican are functional in axon guidance. We also find that LON-2/glypican functions from the epidermal substrate cells to guide axons, and we provide evidence that LON-2/glypican associates with UNC-40/DCC receptor-expressing cells. We propose that LON-2/glypican acts as a modulator of UNC-40/DCC-mediated guidance to fine-tune axonal responses to UNC-6/netrin signals during migration.
Animal migration, Axon guidance, Axon guidance receptors, Axons, Caenorhabditis elegans, Complementary DNA, Neuron migration, Neurons
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Copyright: © 2015 Blanchette et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Biol. 2015 Jul 6;13(7):e1002183. doi: 10.1371/journal.pbio.1002183. eCollection 2015. Link to article on publisher's site
Blanchette C, Perrat PN, Thackeray A, Benard CY. (2015). Glypican Is a Modulator of Netrin-Mediated Axon Guidance. Open Access Articles. https://doi.org/10.1371/journal.pbio.1002183. Retrieved from https://escholarship.umassmed.edu/oapubs/2547
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