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The PrP-Like Proteins Shadoo and Doppel

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Prion Proteins

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 305))

Abstract

An almost unique place within protein databases, twenty-five years of study has underscored the enigmatically subtle role of PrPC in normal cell biology. It seems that PrP has evolved (and survived) to perform a function that does not have a precedent amongst transmembrane cell-surface proteins, perhaps representing a new type of plasma membrane ecosystem. In a context where we await a clarifying insight to unify a panoply of PrPC data into logical molecular framework, the GPI-anchored N-glycosylated Doppel and Sho proteins are tantalizing in that they correspond roughly to the front and back halves of PrPC itself. These molecules may be simpler – and more “understandable” – entities that can be pursued in parallel to PrPC, and could open up the biology of mammalian prion proteins from fresh directions. Dpl has a profound role in successful gametogenesis that warrants close scrutiny and a case for deeper study can be made for Sho, a recently discovered CNS-expressed protein with many parallels to established facets of PrP biochemistry. In an aerial view of biomedical research, Sho and Dpl can be considered as adjacent islands in a prion protein archipelago. As such, the coming years of molecular exploration should be extremely interesting.

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Notes

  1. 1.

    In terms of silent polymorphisms, an L11L change was described in SEG/Pas mice, G108G in CAST/Ei, MAI/Pas, PWK/Pas, and SEG/Pas mice, and G136G in SEG/Pas mice. Conservative missense changes include R86K in wood mouse [34–36]. Of these, L134F can be noted to be in the GPI attachment signal peptide.

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (grants MOP36377), the Alberta Prion Research Institute, the PrionNet Network centre of Excellence and the Alberta Innovates – Health Solutions. DW is supported by the Alberta Prion Research Institute Scholar Program and a Canada Research Chair in Prion Biology. “Three Views of a Secret” and “The Lost World” with acknowledgement and apologies to Jaco Pastorius and Arthur Conan Doyle.

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Authors and Affiliations

  1. Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada

    David Westaway, Nathalie Daude & Serene Wohlgemuth

  2. Department of Biology, McGill University, Montreal, QC, Canada

    Paul Harrison

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  1. David Westaway
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  2. Nathalie Daude
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  3. Serene Wohlgemuth
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Correspondence to David Westaway .

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  1. Adolf-Butenandt-Institute, Abt. Biochemie, Universität München, Schillerstr. 44, München, 80336, Germany

    Jörg Tatzelt

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Westaway, D., Daude, N., Wohlgemuth, S., Harrison, P. (2011). The PrP-Like Proteins Shadoo and Doppel. In: Tatzelt, J. (eds) Prion Proteins. Topics in Current Chemistry, vol 305. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_190

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