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

Victoria Lewis; Vanessa A Johanssen; Peter J Crouch; Genevieve M Klug; Nigel M Hooper; Steven J Collins

Journal article

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

Victoria Lewis, Vanessa A Johanssen, Peter J Crouch, Genevieve M Klug, Nigel M Hooper, Steven J 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 (PrP(C)) is a ubiquitously expressed protein of currently unresolved but potentially diverse function. Of putative relevance to normal biological activity, PrP(C) 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 PrP(C), as well as the selective use of a far-C-terminal anti-PrP antibody, we have identified a new PrP(C) fragment, nominally 'C3', and elaborating existing nomenclature, 'γ-cleavage' as the responsible proteolysis..

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University of Melbourne Researchers

Steven Collins Author Medicine - Royal Melbourne Hospital

Peter Crouch Author Biochemistry and Pharmacology

Vicki Lewis Author Medicine - Royal Melbourne Hospital

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Grants

Awarded by Australian Government National Health and Medical Research Council (NHMRC)

Awarded by Medical Research Council of Great Britain

Awarded by Medical Research Council

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).