Prion protein "gamma-cleavage": Characterizing a novel endoproteolytic processing event

V Lewis; VA Johanssen; PJ Crouch; GM Klug; NM Hooper; SJ Collins

Journal article

Prion protein "gamma-cleavage": Characterizing a novel endoproteolytic processing event

V Lewis, VA Johanssen, PJ Crouch, GM Klug, NM Hooper, SJ Collins

Cellular and Molecular Life Sciences | SPRINGER BASEL AG | Published : 2016

DOI: 10.1007/s00018-015-2022-z

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Abstract

The cellular prion protein (PrPC) is a ubiquitously expressed protein of currently unresolved but potentially diverse function. Of putative relevance to normal biological activity, PrPC is recognized to undergo both α- and β-endoproteolysis, producing the cleavage fragment pairs N1/C1 and N2/C2, respectively. Experimental evidence suggests the likelihood that these processing events serve differing cellular needs. Through the engineering of a C-terminal c-myc tag onto murine PrPC, as well as the selective use of a far-C-terminal anti-PrP antibody, we have identified a new PrPC fragment, nominally 'C3', and elaborating existing nomenclature, 'γ-cleavage' as the responsible proteolysis. Our st..

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University of Melbourne Researchers

Vicki Lewis Author

Peter Crouch Author

Steven Collins Author

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Awarded by University of Melbourne

Funding Acknowledgements

The authors thank Associate Professor Victoria Lawson for her kind gift of the RK13 cells, Professor Charles Weissmann for the Tga20 mice, and the Victorian Brain Bank Network for their assistance in human control brain tissue sampling. This work was supported by an Australian Government National Health and Medical Research Council (NHMRC) Program Grant #628946 (SJC, VL, VJ), Practitioner Fellowship #1005816 (SJC), Training Fellowship #567123 (VL), R. D. Wright Fellowship (CDF2) (PJC) and Project Grant #1061550 (PJC), a University of Melbourne Early Career Researcher Fellowship (VL), the CJD Support Group Network (VL), and the Medical Research Council of Great Britain (G0802189) (NMH).