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First published online April 5, 2005
doi: 10.1242/10.1242/jcs.02296

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DCC association with lipid rafts is required for netrin-1-mediated axon guidance

Zoltán Hérincs^1,*, Véronique Corset^2,*, Nathalie Cahuzac¹, Céline Furne², Valérie Castellani³, Anne-Odile Hueber^1,*, and Patrick Mehlen^2,*,

¹ Death Receptor Signalling Laboratory – Equipe ATIP CNRS, Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR 6543 Centre A. Lacassagne 33 Avenue Valombrose 06189 Nice, France
² Apoptosis, Cancer and Development Laboratory – Equipe labellisée `La Ligue', CNRS FRE 2870, Centre Léon Berard, 69008 Lyon, France
³ Axonal Guidance and Signalling, Molecular and Cellular Genetic Center, CNRS UMR 5534, University of Lyon, 69622 Villeurbanne, France

Authors for correspondence (e-mail: hueber{at}unice.fr; mehlen{at}lyon.fnclcc.fr)

Accepted 31 January 2005

During development, axons migrate long distances in responses to attractive or repulsive signals that are detected by their growth cones. One of these signals is mediated by netrin-1, a diffusible laminin-related molecule that both attracts and repels growth cones via interaction with its receptor DCC (deleted in colorectal cancer). Here we show that DCC in both commissural neurons and immortalized cells, is partially associated with cholesterol- and sphingolipid-enriched membrane domains named lipid rafts. This localization of DCC in lipid rafts is mediated by the palmitoylation within its transmembrane region. Moreover, this raft localization of DCC is required for netrin-1-induced DCC-dependent ERK activation, and netrin-1-mediated axon outgrowth requires lipid raft integrity. Thus, the presence of axon guidance-related receptors in lipid rafts appears to be a crucial pre-requisite for growth cone response to chemo-attractive or repulsive cues.

Key words: DCC, netrin-1, lipid raft, axon outgrowth, palmitoylation

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