Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.

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.
Mesh Terms:
3T3 Cells, Animals, Cell Adhesion Molecules, Cell Line, Cell Size, Culture Techniques, DNA-Binding Proteins, Enzyme Activation, Genes, Reporter, Growth Cones, Humans, Mice, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Nerve Growth Factors, Precipitin Tests, Proto-Oncogene Proteins, Receptors, Cell Surface, Signal Transduction, Spinal Cord, Transcription Factors, Tumor Suppressor Proteins, Two-Hybrid System Techniques, Xenopus, ets-Domain Protein Elk-1
Nature
Date: May. 23, 2002
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