Cellular Prion Protein Promotes Regeneration of Adult Muscle Tissue

Abstract

It is now well established that the conversion of the cellular prion protein, PrP C , into its anomalous conformer, PrP Sc , is central to the onset of prion disease. However, both the mechanism of prion-related neurodegeneration and the physiologic role of PrP C 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 PrP C and have been related to PrP C 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, PrP C . Using morphometric and biochemical parameters, we provide compelling evidence that the absence of PrP C 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 PrP C expression completely rescued the muscle phenotype evidenced in the absence of PrP C .

The evaluation of 23-bp and 12-bp insertion/deletion within the PRNP gene and their effects on growth traits in healthy Chinese native cattle breeds

“…Up to date, de Vries et al (2004) proved significant effects for the PrP genotype on both conformation score in Texel sheep and muscle mass score in German Black Headed Mutton sheep. In addition, Stella et al (2010) found that the PrPs control the release of TNF-α factor which involved in muscle differentiation and downstream signalling pathways that affect the longevity of cells in adult muscles in many species of mammals; Smith et al (2011) cited that the low level of PrP is associated with decreased muscle mass of rat. Isler et al (2006) showed a correlation between the variation in PrP genotypes and the longissimus muscle depth of Dorset × Romanov sheep.…”

Prion and TNFα: TAC(E)it agreement between the prion protein and cell signaling

“…13 To obtain this data, our strategy considered the use of an in vivo paradigm novel to the field of PrP C biology. It consisted in acutely damaging the hind limb tibialis anterior muscle of adult mice expressing or not PrP C , and then in following regeneration from muscle precursors cells.…”

Physiological role of prions in regulation of Ca2+-transport and neurodegenerative diseases

“…Наприклад, показано, що у PrP-нокаутованих мишей порушений процес утворення гемопоетичних лімфоци-тів [112] і пригнічена регенерація скелетних м'язів [94].…”