Cellular Biology of Prion Diseases

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Clinical Microbiology Reviews, July 1999, p. 429-444, Vol. 12, No. 3
0893-8512/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cellular Biology of Prion Diseases

David A. Harris^*

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on publichealth and because they exemplify a novel mechanism of infectivityand biological information transfer. These diseases are causedby conformational conversion of a normal host glycoprotein (PrP^C) into an infectious isoform (PrP^Sc) that is devoid of nucleic acid. This review focuses on the currentunderstanding of prion diseases at the cell biological level.The characteristics of the diseases are introduced, and a briefhistory and description of the prion hypothesis are given. Informationis then presented about the structure, expression, biosynthesis,and possible function of PrP^C, as well as its posttranslational processing, cellular localization,and trafficking. The latest findings concerning PrP^Sc are then discussed, including cell culture systems used to generatethis pathogenic isoform, the subcellular distribution of the protein,its membrane attachment, proteolytic processing, and its kineticsand sites of synthesis. Information is also provided on molecularmodels of the PrP^C $right-arrow$ PrP^Sc conversion reaction and the possible role of cellular chaperones.The review concludes with suggestions of several important avenuesfor futureinvestigation.

^* Mailing address: Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Ave.,St. Louis, MO 63110. Phone: (314) 362-4690. Fax: (314) 362-7463.E-mail: dharris{at}cellbio.wustl.edu.

Clinical Microbiology Reviews, July 1999, p. 429-444, Vol. 12, No. 3
0893-8512/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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