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Interactions of Prion Protein With Intracellular Proteins: So Many Partners and no Consequences?

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Abstract

Prion protein (PrP) plays a key role in the pathogenesis of transmissible spongiform encephalopathies (TSEs)—fatal diseases of the central nervous system. Its physiological function as well as exact role in neurodegeneration remain unclear, hence screens for proteins interacting with PrP seem to be the most promising approach to elucidating these issues. PrP is mostly a plasma membrane-anchored extracellular glycoprotein and only a small fraction resides inside the cell, yet the number of identified intracellular partners of PrP is comparable to that of its membranal or extracellular interactors. Since some TSEs are accompanied by significantly increased levels of cytoplasmic PrP and this fraction of the protein has been found to be neurotoxic, it is of particular interest to characterize the intracellular interactome of PrP. It seems reasonable that at elevated cytoplasmic levels, PrP may exert cytotoxic effect by affecting the physiological functions of its intracellular interactors. This review is focused on the cytoplasmic partners of PrP along with possible consequences of their binding.

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Abbreviations

Bcl-2:

B-cell lymphoma 2 protein

BSE:

Bovine spongiform encephalopathy

C1:

N-terminally truncated form of PrP encompassing residues ~110/112–231

C2:

N-terminally truncated form of PrP encompassing residues ~90/91–231

CaMKIIα:

Calcium/calmodulin-dependent protein kinase α type II

CJD:

Creutzfeldt–Jakob disease

CK2:

Casein kinase 2

CtmPrP:

Transmembrane form of PrP with the C-terminus residing in the lumen of ER

CWD:

Chronic wasting disease

cyPrP, cytPrP, cytoPrP:

PrP residing entirely in the cytosol

ER:

Endoplasmic reticulum

FFI:

Fatal familial insomnia

GFAP:

Glial fibrillary acidic protein

GPI:

Glycosylphosphatidylinositol

Grb2:

Growth factor receptor-bound protein 2

GSS:

Gerstmann–Sträussler–Scheinker disease

HEK:

Human embryonic kidney cells

hnRNP:

Heterogeneous nuclear ribonucleoprotein

Hsp:

Heat shock protein

MAPs:

Microtubule-associated proteins

Mgrn:

Mahogunin

NLS:

Nuclear localization signal

NRAGE:

Neurotrophin receptor-interacting MAGE homolog

Nrf2:

Nuclear factor erythroid 2-related factor 2

NtmPrP:

Transmembrane form of PrP with the N-terminus residing in the lumen of ER

OR:

Octapeptide repeats

PK:

Proteinase K

Prnp :

Prion protein gene

PrP:

Prion protein

PrPC :

Cellular form of PrP

PrPSc :

Scrapie form of PrP

rPrP:

Recombinant PrP

SP:

Signal peptide

TM:

Transmembrane domain

TSE:

Transmissible spongiform encephalopathy

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Acknowledgments

The author thanks Dr. Hanna Nieznanska for critical reading of the manuscript and helpful comments. This work was supported by a statutory grant to the Nencki Institute of Experimental Biology from the Ministry of Science and Higher Education.

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  1. Department of Biochemistry, Polish Academy of Sciences, Nencki Institute of Experimental Biology, 3 Pasteur St, Warsaw, 02 093, Poland

    Krzysztof Nieznanski

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Nieznanski, K. Interactions of Prion Protein With Intracellular Proteins: So Many Partners and no Consequences?. Cell Mol Neurobiol 30, 653–666 (2010). https://doi.org/10.1007/s10571-009-9491-2

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