期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 40, 期 2, 页码 242-248出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.10.012
关键词
Prion protein; Proteolysis; Lipid raft; Endocytosis; Golgi
资金
- Medical Research Council
- Biotechnology and Biological Research Council of Great Britain
- Wellcome Trust
- MRC [G9824728] Funding Source: UKRI
- Medical Research Council [G9824728] Funding Source: researchfish
Endoproteolysis of the cellular prion protein (PrPC) modulates both the normal function of the protein and the pathogenesis of the neurodegenerative prion diseases. PrPC undergoes alpha-cleavage to generate the N-terminally truncated fragment C1. Utilizing various constructs of PrPC expressed in human neuroblastoma cells we investigated the subcellular compartment where a-cleavage occurs. Cl was detected at the cell surface and the generation of Cl occurred in mutants of PrPC incapable of Cu2+-mediated endocytosis. A transmembrane-anchored form that is not lipid raft-localised, as well as a secreted construct lacking the glycosyl-phosphatidylinositol membrane anchor, were also subject to alpha-cleavage. However, when this transmembrane-anchored form was modified with an endoplasmic reticulum retention motif, C1 was not formed. Inhibition of protein export from the Golgi by temperature block increased the amount of C1. Our data thus demonstrate that the a-cleavage of PrPC occurs predominantly in a raft-independent manner in a late compartment of the secretory pathway. (C) 2008 Elsevier Inc. All rights reserved.
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