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KONDOH/MACMILLAN1 P0 [7 }0 R, E; c2 f! n
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A target of blood pressure–lowering drugs harbors the unexpected ability to release GPI-anchored proteins. Gen Kondoh (Kyoto University, Kyoto, Japan), Junji Takeda (Osaka University, Osaka, Japan), and colleagues reveal that this enzyme, ACE, is both a peptidase and GPIase in one multifunctional package.ACE's peptidase activity is well studied〞it cleaves and activates angiotensin, which up-regulates blood pressure through hormonal changes. But Kondoh did not expect to find ACE in his screen for proteins that release GPI-anchored proteins from the cell surface.
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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.
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) e4 k& |+ \1 N- b! X OAs 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.3 X5 y1 F7 T4 ]' l4 [
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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.. J6 X; d3 x0 |9 M& P( N! M
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Reference:
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Kondoh, G., et al. 2005. Nat. Med. doi:10.1038/nm1179(Sperm–egg binding (left) is lost when AC) |
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发表于 2009-3-6 08:53
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