TY - JOUR
T1 - Draxin inhibits axonal outgrowth through the netrin receptor dcc
AU - Ahmed, Giasuddin
AU - Shinmyo, Yohei
AU - Ohta, Kunimasa
AU - Islam, Shahidul M.
AU - Hossain, Mahmud
AU - Naser, Iftekhar Bin
AU - Riyadh, M. Asrafuzzaman
AU - Su, Yuhong
AU - Zhang, Sanbing
AU - Tessier-Lavigne, Marc
AU - Tanaka, Hideaki
PY - 2011/9/28
Y1 - 2011/9/28
N2 - 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.
AB - 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.
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U2 - 10.1523/JNEUROSCI.0943-11.2011
DO - 10.1523/JNEUROSCI.0943-11.2011
M3 - Article
C2 - 21957262
AN - SCOPUS:80053238957
SN - 0270-6474
VL - 31
SP - 14018
EP - 14023
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 39
ER -