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Mol. Cell. Biol. 30 (20): 4864-4876

Copyright © 2010 by the American Society for Microbiology. All rights reserved.

Cellular Prion Protein Promotes Regeneration of Adult Muscle Tissue {triangledown} ,{dagger}

Roberto Stella,1 Maria Lina Massimino,2 Marco Sandri,3,4 M. Catia Sorgato,1,2, and Alessandro Bertoli1*

Department of Biological Chemistry,1 CNR Institute of Neuroscience,2 Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35131 Padua, Italy,3 Dulbecco Telethon Institute-Venetian Institute of Molecular Medicine, Via G. Orus, 2, 35129 Padua, Italy4

Received for publication 6 August 2009. Revision received 2 September 2009. Accepted for publication 22 July 2010.

Abstract: It is now well established that the conversion of the cellular prion protein, PrPC, into its anomalous conformer, PrPSc, is central to the onset of prion disease. However, both the mechanism of prion-related neurodegeneration and the physiologic role of PrPC are still unknown. The use of animal and cell models has suggested a number of putative functions for the protein, including cell signaling, adhesion, proliferation, and differentiation. Given that skeletal muscles express significant amounts of PrPC and have been related to PrPC pathophysiology, in the present study, we used skeletal muscles to analyze whether the protein plays a role in adult morphogenesis. We employed an in vivo paradigm that allowed us to compare the regeneration of acutely damaged hind-limb tibialis anterior muscles of mice expressing, or not expressing, PrPC. Using morphometric and biochemical parameters, we provide compelling evidence that the absence of PrPC significantly slows the regeneration process compared to wild-type muscles by attenuating the stress-activated p38 pathway, and the consequent exit from the cell cycle, of myogenic precursor cells. Demonstrating the specificity of this finding, restoring PrPC expression completely rescued the muscle phenotype evidenced in the absence of PrPC.


* Corresponding author. Mailing address: University of Padua, Department of Biological Chemistry, Viale G. Colombo, 3, 35131 Padua, Italy. Phone: 39 049 8276150. Fax: 39 049 8073310. E-mail: alessandro.bertoli{at}unipd.it

{triangledown} Published ahead of print on 2 August 2010.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.



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