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KONDOH/MACMILLAN4 C4 X6 v) a, A" G- L& r
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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.) l+ k; y' Y: k9 `, w
: ~% z: {$ N! X1 IGPI 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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3 F* a& X5 _( Z3 s! l3 i1 qAs 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.& A% P5 \: r* C
M/ T3 I1 ~# R. HAnchored 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.
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Reference:2 ^/ k1 O C$ p8 f
5 ^8 F: @, }' R6 `$ u6 [$ w! UKondoh, 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
发表于 2009-12-6 17:01
