DCC association with lipid rafts is required for netrin-1-mediated axon guidance.
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.
Hérincs
Zoltán
Z
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.
Corset
Véronique
V
Cahuzac
Nathalie
N
Furne
Céline
C
Castellani
Valérie
V
Hueber
Anne-Odile
AO
Mehlen
Patrick
P
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D003463:Cues; D000075389:DCC Receptor; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075388:Netrin-1; D019308:Palmitic Acid / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000196:embryology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D008563:Membrane Lipids; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D019308:Palmitic Acid; D048049:Extracellular Signal-Regulated MAP Kinases