Journal Article

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

Stein, Elke, Corset, Véronique, Llambi, Fabien, Tessier-Lavigne, Marc, Mehlen, Patrick, Forcet, Christelle, Pays, Laurent

2002

Overview

Neuronal growth cones are guided to their targets by attractive and repulsive guidance cues 1 . In mammals, netrin-1 is a bifunctional cue, attracting some axons and repelling others 2 , 3 , 4 , 5 . Deleted in colorectal cancer (Dcc) is a receptor for netrin-1 that mediates its chemoattractive effect on commissural axons 6 , 7 , 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.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: 3T3 Cells / Animals / Biological and medical sciences / Cell Adhesion Molecules - genetics / Cell Adhesion Molecules - metabolism / Cell Line / Cell physiology / Cell Size - drug effects / Colorectal cancer / Colorectal carcinoma / Culture Techniques / Dcc gene / DCC Receptor / DNA-Binding Proteins / Enzyme Activation - drug effects / ERK1 protein / ERK2 protein / ets-Domain Protein Elk-1 / Fundamental and applied biological sciences. Psychology / Genes, Reporter / Growth Cones - drug effects / Growth Cones - enzymology / Growth Cones - metabolism / Humanities and Social Sciences / Humans / letter / Mammals / Mice / Mitogen-Activated Protein Kinase Kinases - metabolism / Mitogen-Activated Protein Kinases - antagonists & inhibitors / Mitogen-Activated Protein Kinases - genetics / Mitogen-Activated Protein Kinases - metabolism / Molecular and cellular biology / multidisciplinary / Nerve Growth Factors - metabolism / Nerve Growth Factors - pharmacology / Netrin-1 / Neurons / Precipitin Tests / Proteins / Proto-Oncogene Proteins - metabolism / Receptors, Cell Surface / Science / Science (multidisciplinary) / Signal transduction / Signal Transduction - drug effects / Spinal Cord - cytology / Spinal Cord - drug effects / Spinal Cord - growth & development / Transcription Factors / Tumor Suppressor Proteins - genetics / Tumor Suppressor Proteins - metabolism / Two-Hybrid System Techniques / Xenopus