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

J. Biol. Chem., Vol. 282, Issue 50, 36525-36533, December 14, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/50/36525    most recent M705620200v1 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 Lee, K. S. Articles by Caughey, B. Search for Related Content PubMed PubMed Citation Articles by Lee, K. S. Articles by Caughey, B. Social Bookmarking                      What's this?

Hemin Interactions and Alterations of the Subcellular Localization of Prion Protein^*

From the Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840

Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrP^C). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrP^C. Accordingly, we evaluated PrP^C interactions with hemin. When hemin (3–10 µM) was added to the medium of cultured cells, clusters of PrP^C formed on the cell surface, and the detergent solubility of PrP^C decreased. The addition of hemin also induced PrP^C internalization and turnover. The ability of hemin to bind directly to PrP^C was demonstrated by hemin-agarose affinity chromatography and UV-visible spectroscopy. Multiple hemin molecules bound primarily to the N-terminal third of PrP^C, with reduced binding to PrP^C lacking residues 34–94. These hemin-PrP^C interactions suggest that PrP^C may participate in hemin homeostasis, sensing, and/or uptake and that hemin might affect PrP^C functions.

Received for publication, July 9, 2007 , and in revised form, September 24, 2007.

^* This work was supported by the Intramural Research Program of the NIAID, National Institutes of Health. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ To whom correspondence should be addressed: Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, MT 59840. Tel.: 406-363-9264; Fax: 406-363-9286; E-mail: bcaughey{at}nih.gov.

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

This article has been cited by other articles:

				F. A. Caetano, M. H. Lopes, G. N. M. Hajj, C. F. Machado, C. Pinto Arantes, A. C. Magalhaes, M. D. P. B. Vieira, T. A. Americo, A. R. Massensini, S. A. Priola, et al. Endocytosis of Prion Protein Is Required for ERK1/2 Signaling Induced by Stress-Inducible Protein 1 J. Neurosci., June 25, 2008; 28(26): 6691 - 6702. [Abstract] [Full Text] [PDF]