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KONDOH/MACMILLAN' m4 i; y1 {, L, u+ s+ u" _/ B/ a, A/ X, ~
4 R/ G3 y7 ~; ~3 H8 v8 AA 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.8 D, m& ^! w) q
, U8 a$ Q' z0 n" l& e, c( V6 gAs 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 n7 z% D& p* l
: L- |& b: ?& cAnchored 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.. s+ W* m7 o" }
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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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