HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 1, 317-325, January 7, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/1/317    most recent M410649200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Ma, J. Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Ma, J. Social Bookmarking                      What's this?

Calpain and Other Cytosolic Proteases Can Contribute to the Degradation of Retro-translocated Prion Protein in the Cytosol^*

Xinhe Wang, Fei Wang, Man-Sun Sy, and Jiyan Ma¶

From the Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210 and the Institute of Pathology and Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44120

PrP, a cell surface-localized N-linked glycoprotein, is required for the pathogenesis of prion diseases. Recent studies have revealed that prion protein (PrP) becomes neurotoxic and prone to aggregation when it is in the cytosol, suggesting that cytosolic PrP may play a role in the pathogenesis of prion disease. Retro-translocation of PrP from the endoplasmic reticulum to the cytosol for proteasome degradation offers a natural route for PrP to enter the cytosol, but whether PrP is subject to retrotranslocation is controversial. In this study, we investigated the metabolism of endogenous wild-type PrP in several cell lines and in primary mouse cortical neurons. Our results suggest that a portion of the endogenous wild-type PrP is retro-translocated to the cytosol and degraded by the proteasome. Moreover, we also found that calpain and other cytosolic proteases could degrade PrP in the cytosol when the proteasome activity is compromised. These results provide the foundation for the hypothesis that cytosolic PrP may be involved in the pathogenesis of prion disease.

Received for publication, September 15, 2004 , and in revised form, November 2, 2004.

^* This work was supported by a grant from the Ellison Medical Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 614-688-0408; Fax: 614-292-4118; E-mail: ma.131{at}osu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Ashok and R. S. Hegde Retrotranslocation of Prion Proteins from the Endoplasmic Reticulum by Preventing GPI Signal Transamidation Mol. Biol. Cell, August 1, 2008; 19(8): 3463 - 3476. [Abstract] [Full Text] [PDF]

				R. Linden, V. R. Martins, M. A. M. Prado, M. Cammarota, I. Izquierdo, and R. R. Brentani Physiology of the Prion Protein Physiol Rev, April 1, 2008; 88(2): 673 - 728. [Abstract] [Full Text] [PDF]

				E. M. Norstrom, M. F. Ciaccio, B. Rassbach, R. Wollmann, and J. A. Mastrianni Cytosolic Prion Protein Toxicity Is Independent of Cellular Prion Protein Expression and Prion Propagation J. Virol., March 15, 2007; 81(6): 2831 - 2837. [Abstract] [Full Text] [PDF]

				A. Orsi, L. Fioriti, R. Chiesa, and R. Sitia Conditions of Endoplasmic Reticulum Stress Favor the Accumulation of Cytosolic Prion Protein J. Biol. Chem., October 13, 2006; 281(41): 30431 - 30438. [Abstract] [Full Text] [PDF]

				X. Wang, F. Wang, L. Arterburn, R. Wollmann, and J. Ma The Interaction between Cytoplasmic Prion Protein and the Hydrophobic Lipid Core of Membrane Correlates with Neurotoxicity J. Biol. Chem., May 12, 2006; 281(19): 13559 - 13565. [Abstract] [Full Text] [PDF]

				L. Fioriti, S. Dossena, L. R. Stewart, R. S. Stewart, D. A. Harris, G. Forloni, and R. Chiesa Cytosolic Prion Protein (PrP) Is Not Toxic in N2a Cells and Primary Neurons Expressing Pathogenic PrP Mutations J. Biol. Chem., March 25, 2005; 280(12): 11320 - 11328. [Abstract] [Full Text] [PDF]