No abstract

PrPC , the normal isoform of the prion component PrP Sc , is a 33-35-kDa glycophosphatidylinositol-anchored glycoprotein expressed in the plasma membrane of many cells and especially in the brain. The specific role of PrP C is unknown, although lately it has been shown to bind copper specifically. We show here that PrP C is present even in mature sperm cells, a polarized cell that retains only the minimal components required for DNA delivery, movement, and energy production. As opposed to PrP C in other cells, PrP in ejaculated sperm cells was truncated in its C terminus in the vicinity of residue 200. Sperm PrP, although membrane-bound, was not released by phosphatidylinositol phospholipase C as well as not localized in cholesterol-rich microdomains (rafts). Although no infertility was reported for PrP-ablated mice in normal situations, our results suggest that sperm cells originating from PrP-ablated mice were significantly more susceptible to high copper concentrations than sperm from wild type mice, allocating a protective role for PrP in specific stress situations related to copper toxicity. Since the functions performed by proteins in sperm cells are limited, these cells may constitute an ideal system to elucidate the function of PrP C .

These data argue that the E200K mutation alone is sufficient to cause prion disease and does so in an age-dependent manner.

BACKGROUND AND PURPOSE:Human prion diseases are known to cause gray matter degeneration in specific cerebral structures, but evidence for white matter involvement is scarce. We used DTI to test the hypothesis that white matter integrity is disrupted in human CJD during the early stages of the disease.

No abstract