Draxin inhibits axonal outgrowth through the netrin receptor dcc

Giasuddin Ahmed, Yohei Shinmyo, Kunimasa Ohta, Shahidul M. Islam, Mahmud Hossain, Iftekhar Bin Naser, M. Asrafuzzaman Riyadh, Yuhong Su, Sanbing Zhang, Marc Tessier-Lavigne, Hideaki Tanaka

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Abstract

Draxin, a recently identified axon guidance protein, is essential for the formation of forebrain commissures, and can mediate repulsion of netrin-stimulated spinal commissural axons. Here, we report that draxin binds multiple netrin receptors: DCC (deleted in colorectal cancer), Neogenin, UNC5s (H1, H2, H3), and DSCAM (Down's syndrome cell adhesion molecule). Since draxin and Dcc knockouts showed similar phenotype in forebrain commissures formation, we show here the functional importance of draxin/DCC interaction. Draxin interacts with subnanomolar affinity to the netrin receptor DCC, in a region of DCC distinct from its netrin-binding domain. In vitro, neurite outgrowth from cortical and olfactory bulb explants of Dcc knock-out mice is significantly less inhibited by draxin, when compared with neurites from explants of wild-type mice. Furthermore, in comparison with wild-type mice, the growth cone collapse in response to draxin is largely abolished in Dcc-deficient cortical neurons. In vivo, double heteros of draxin/Dcc mice show markedly higher frequency of complete agenesis of corpus callosum than either of the single hetero. These results identifyDCCas a convergent receptor for netrinanddraxin in axon growthandguidance.

Original languageEnglish (US)
Pages (from-to)14018-14023
Number of pages6
JournalJournal of Neuroscience
Volume31
Issue number39
DOIs
StatePublished - Sep 28 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ahmed, G., Shinmyo, Y., Ohta, K., Islam, S. M., Hossain, M., Naser, I. B., Riyadh, M. A., Su, Y., Zhang, S., Tessier-Lavigne, M., & Tanaka, H. (2011). Draxin inhibits axonal outgrowth through the netrin receptor dcc. Journal of Neuroscience, 31(39), 14018-14023. https://doi.org/10.1523/JNEUROSCI.0943-11.2011