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First published online December 31, 2008
doi: 10.1242/10.1242/jcs.030338

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Binding of laminin-1 to monosialoganglioside GM1 in lipid rafts is crucial for neurite outgrowth

¹ Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo, Japan
² Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
³ Institute for Environmental and Gender Specific Medicine, Juntendo University School of Medicine, Tokyo, Japan
⁴ Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan
⁵ Sphingolipid Functions Laboratory, RIKEN Frontier Research System, Saitama, Japan
⁶ Shriners Hospitals for Children, Research Center, Portland, OR 97201, USA
⁷ Laboratory of Cell and Developmental Biology, NIDCR, NIH, Bethesda, MD 20892, USA

^* Author for correspondence (e-mail: ehirasaw{at}med.juntendo.ac.jp)

Accepted 8 September 2008

Laminin-1, an extracellular matrix molecule, promotes neurite outgrowth through the interaction of integrin and actin. Monosialoganglioside GM1 in the lipid rafts associates with and activates the NGF receptor TrkA, and enhances neurite outgrowth. However, the role of GM1 in laminin-1-induced neurite outgrowth was still unclear. Here, we describe that laminin-1 binds to GM1 through a carbohydrate moiety and a specific conformation of GM1, induces focal formation of large clusters of GM1, and enhances the relocation of TrkA in the membrane of dorsal root ganglion (DRG) and PC12 cells. We found that laminin-1-mediated clustering of GM1 causes the translocation and enrichment of β1 integrin in lipid rafts – where TrkA colocalizes with β1 integrin – and the activation of Lyn, Akt and MAPK to promote the outgrowth of neurites. Our results suggest that the binding of laminin-1 to GM1 facilitates the formation of a focal microdomain in the membrane, and enhances signal transduction that promotes neurite outgrowth by linking NGF-TrkA signaling with the laminin-integrin signaling pathways.

Key words: GM1, Integrin, Laminin, Lipid rafts, Neurite outgrowth

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