Research Article 773 LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein Celia J. Parkyn1, Esmeralda G. M. Vermeulen1, Roy C. Mootoosamy1, Claire Sunyach1,*, Christian Jacobsen2, Claus Oxvig2, Søren Moestrup2, Qiang Liu3, Guojun Bu3, Angela Jen1 and Roger J. Morris1,‡ 1Kingʼs College London, Wolfson Centre for Age Related Disease, Guyʼs Campus, London SE1 1UL, UK 2Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark 3Department of Pediatrics, Washington University School of Medicine, St Louis Childrenʼs Hospital, St Louis MO 63110, USA *Present address: IPMC du CNRS, UPR411, 660 Route del Lucioles, 06560 Valbonne, France ‡Author for correspondence (e-mail:
[email protected]) Accepted 19 December 2007 Journal of Cell Science 121, 773-783 Published by The Company of Biologists 2008 doi:10.1242/jcs.021816 Summary The trafficking of normal cellular prion protein (PrPC) is trafficking of PrPC to the neuronal surface. PrPC and LRP1 believed to control its conversion to the altered conformation can be co-immunoprecipitated from the endoplasmic reticulum (designated PrPSc) associated with prion disease. Although in normal neurons. The N-terminal domain of PrPC binds to anchored to the membrane by means of purified human LRP1 with nanomolar affinity, even in the glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly presence of 1 M of the LRP-specific chaperone, receptor- and constitutively endocytosed by means of coated pits, a associated protein (RAP). Taken together, these data argue that property dependent upon basic amino acids at its N-terminus. LRP1 controls both the surface, and biosynthetic, trafficking Here, we show that low-density lipoprotein receptor-related of PrPC in neurons.