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XB-ART-7201
Nature 2002 May 23;4176887:443-7. doi: 10.1038/nature748.
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Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.

Forcet C , Stein E , Pays L , Corset V , Llambi F , Tessier-Lavigne M , Mehlen P .


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Neuronal growth cones are guided to their targets by attractive and repulsive guidance cues. In mammals, netrin-1 is a bifunctional cue, attracting some axons and repelling others. Deleted in colorectal cancer (Dcc) is a receptor for netrin-1 that mediates its chemoattractive effect on commissural axons, but the signalling mechanisms that transduce this effect are poorly understood. Here we show that Dcc activates mitogen-activated protein kinase (MAPK) signalling, by means of extracellular signal-regulated kinase (ERK)-1 and -2, on netrin-1 binding in both transfected cells and commissural neurons. This activation is associated with recruitment of ERK-1/2 to a Dcc receptor complex. Inhibition of ERK-1/2 antagonizes netrin-dependent axon outgrowth and orientation. Thus, activation of MAPK signalling through Dcc contributes to netrin signalling in axon growth and guidance.

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Species referenced: Xenopus
Genes referenced: dcc mapk1 ntn1