GPI deficiencies cause severe problems in fertility and development. GPI also links the prion protein to membranes. But the activities that release these linkages were not well-known. Now, Kondoh shows that a region of ACE distinct from its peptidase domain has this ability. Soluble prion protein protects against scrapie, so ACE, especially a peptidase-inactive form, may be a useful disease treatment.
As ACE was found in a mouse testicular preparation, the group examined sperm lacking the ACE GPIase activity. The mutant sperm were infertile and unable to release several GPI-linked proteins from their surface.
Anchored proteins were partly protected from ACE cleavage if they were in lipid rafts. By keeping GPI-linked fertilization factors in rafts, their release could be delayed until the raft disruption that occurs during capacitation.