A C-terminal-truncated PrP Isoform Is Present in Mature Sperm

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 .

Expression of Prnp mRNA (Prion Protein Gene) in Mouse Spermatogenic Cells

“…PrP c is classified as a GPI-anchored glycoprotein, which exists on the cell membrane surface via GPI [26]. It has been shown that the structure of PrP c in mature spermatozoa differs from immature ones [25]. PrP c was not separated from epididymal and ejaculated spermatozoa processed by PIPLC ( p h o s p h a t i d y l i n o s i t o l p h o s p h o l i p a s e C ) .…”

Goat PRND expression pattern suggests its involvement in early sex differentiation

“…PRNP is expressed in most of the tissues analyzed so far with the highest amounts present in the brain. In mice and ram, Prnp was found to be expressed in germ cells (Shaked et al, 1999;Weber et al, 2003;Ecroyd et al, 2004), but its invalidation in mice does not induce a fertility-associated phenotype (Bueler et al, 1992).…”

Male Infertility and DNA Damage in Doppel Knockout and Prion Protein/Doppel Double-Knockout Mice

“…All Prnp Ϫ/Ϫ mouse lines reproduce normally, suggesting that PrP C expression is not essential for normal reproductive function, or that a related protein compensates for the loss of PrP C function in these mice. However it has been shown that PrP C can protect sperm from the detrimental effects of copper toxicity and associated oxidative stress, 24 and because of the biochemical similarities between PrP C and Dpl it is not unreasonable to suggest Dpl may play a similar role.…”

“…23,24 PrP C is found in epididymal cells and truncated isoforms have been identified on ejaculated human spermatozoa, although the nature of the truncation is unclear, with the first report describing a C-terminally truncated isoform and the second an N-terminal truncation. All Prnp Ϫ/Ϫ mouse lines reproduce normally, suggesting that PrP C expression is not essential for normal reproductive function, or that a related protein compensates for the loss of PrP C function in these mice.…”