Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth

doi:10.1083/jcb.200409127

Published 25 April 2005. doi:10.1083/jcb.200409127
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 2, 341-354

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Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59^fyn and to enhance neurite outgrowth

Antonella Santuccione¹^,2, Vladimir Sytnyk¹, Iryna Leshchyns'ka¹, and Melitta Schachner¹

¹ Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
² Department of Oncology and Neuroscience, Gabriele d'Annunzio University, 66100 Chieti, Italy

Correspondence to Melitta Schachner: melitta.schachner{at}zmnh.uni-hamburg.de

In spite of advances in understanding the role of the cellularprion protein (PrP) in neural cell interactions, the mechanismsof PrP function remain poorly characterized. We show that PrPinteracts directly with the neural cell adhesion molecule (NCAM)and associates with NCAM at the neuronal cell surface. Bothcis and trans interactions between NCAM at the neuronal surfaceand PrP promote recruitment of NCAM to lipid rafts and therebyregulate activation of fyn kinase, an enzyme involved in NCAM-mediatedsignaling. Cis and trans interactions between NCAM and PrP promoteneurite outgrowth. When these interactions are disrupted inNCAM-deficient and PrP-deficient neurons or by PrP antibodies,NCAM/PrP-dependent neurite outgrowth is arrested, indicatingthat PrP is involved in nervous system development cooperatingwith NCAM as a signaling receptor.

A. Santuccione, V. Sytnyk, and I. Leshchyns'ka contributed equallyto this paper.

Abbreviations used in this paper: GPI, glycosylphosphatidylinositol;NCAM, neural cell adhesion molecule; PrP, prion protein; PSA,polysialic acid; RPTP ${alpha}$ , receptor type protein phosphatase ${alpha}$ .

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