In spite of advances in understanding the role of the cellular prion protein (PrP) in neural cell interactions, the mechanisms of PrP function remain poorly characterized. We show that PrP interacts directly with the neural cell adhesion molecule (NCAM) and associates with NCAM at the neuronal cell surface. Both cis and trans interactions between NCAM at the neuronal surface and PrP promote recruitment of NCAM to lipid rafts and thereby regulate activation of fyn kinase, an enzyme involved in NCAM-mediated signaling. Cis and trans interactions between NCAM and PrP promote neurite outgrowth. When these interactions are disrupted in NCAM-deficient and PrP-deficient neurons or by PrP antibodies, NCAM/PrP-dependent neurite outgrowth is arrested, indicating that PrP is involved in nervous system development cooperating with NCAM as a signaling receptor.
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25 April 2005
Article|
April 25 2005
Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth
Antonella Santuccione,
Antonella Santuccione
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
2Department of Oncology and Neuroscience, Gabriele d'Annunzio University, 66100 Chieti, Italy
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Vladimir Sytnyk,
Vladimir Sytnyk
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
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Iryna Leshchyns'ka,
Iryna Leshchyns'ka
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
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Melitta Schachner
Melitta Schachner
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
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Antonella Santuccione
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
2Department of Oncology and Neuroscience, Gabriele d'Annunzio University, 66100 Chieti, Italy
Vladimir Sytnyk
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
Iryna Leshchyns'ka
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
Melitta Schachner
1Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
Correspondence to Melitta Schachner: [email protected]
A. Santuccione, V. Sytnyk, and I. Leshchyns'ka contributed equally to this paper.
Abbreviations used in this paper: GPI, glycosylphosphatidylinositol; NCAM, neural cell adhesion molecule; PrP, prion protein; PSA, polysialic acid; RPTPα, receptor type protein phosphatase α.
Received:
September 21 2004
Accepted:
March 11 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (2): 341–354.
Article history
Received:
September 21 2004
Accepted:
March 11 2005
Citation
Antonella Santuccione, Vladimir Sytnyk, Iryna Leshchyns'ka, Melitta Schachner; Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth . J Cell Biol 25 April 2005; 169 (2): 341–354. doi: https://doi.org/10.1083/jcb.200409127
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