A C-terminal-truncated PrP isoform is present in mature sperm

PrPC, the normal isoform of the prion component PrPSc, is a 33-35-kDa glyco phosphatidylinositol-anchored glycoprotein expressed in the plasma membrane of many cells and especially in the brain. The specific role of PrPC is un known, although lately it has been shown to bind copper specifically. We sh ow here that PrPC is present even in mature sperm cells, a polarized cell t hat retains only the minimal components required for DNA delivery, movement , and energy production, As opposed to PrPC in other cells, PrP in ejaculat ed sperm cells was truncated in its C terminus in the vicinity of residue 2 00, Sperm PrP, although membrane-bound, was not released by phosphatidylino sitol phospholipase C as web as not localized in cholesterol-rich microdoma ins (rafts), Although no infertility was reported for PrP-ablated mice in n ormal situations, our results suggest that sperm cells originating from PrP -ablated mice were significantly more susceptible to high copper concentrat ions than sperm from wild type mice, allocating a protective role for PrP i n specific stress situations related to copper toxicity. Since the function s performed by proteins in sperm cells are limited, these cells may constit ute an ideal system to elucidate the function of PrPC.