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Supersensitive phospholipid sensing [复制链接]

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发表于 2009-3-6 08:53 |只看该作者 |正序浏览 |打印
Alysine-laden sensor makes an actin regulator ultrasensitive to phospholipid levels, according to Venizelos Papayannopoulos, Wendell Lim (University of California, San Francisco, CA), and colleagues.
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Phospholipids, particularly PIP2, are activators of N-WASP〞an Arp2/3 regulator that turns on actin polymerization. None of the common PIP-binding domains (e.g., Pleckstrin Homology or Phox domains) are found in N-WASP. Instead, a region of 10 basic residues (the B motif) binds to the phospholipids. The new research reveals that this conglomerate of positive charges turns N-WASP into an all-or-nothing switch in response to changing PIP2 density.+ L( X/ V: P5 Q) G  k7 b. n( `

! j: ?& o5 ?  K! I- D2 TAt 10% PIP2, N-WASP bound tenfold more strongly to vesicles than it did at 2% PIP2. Even sharper effects from lipid density were seen in actin polymerization assays. Cholesterol, which recruits PIP2 to lipid rafts, lowered the activation threshold, suggesting that local density, not overall concentration, of the phospholipid is key. "Polymerization must be spatially precise," says Lim. "Having N-WASP respond to the spatial organization of input molecules adds a high level of precision."$ _% I3 d$ j/ P  m2 e  g& K1 I$ K

( f2 [1 G* z. i7 rAnother activator of N-WASP is Cdc42, which the team found significantly lowered the level of PIP2 required for N-WASP activity. This ability may allow N-WASP to be turned on without altering cellular PIP2 levels.
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9 q2 \. }1 l# `* N( h4 eThe activation threshold is determined by the number of basic residues in the B motif〞more lysines allowed N-WASP to be activated at a lower PIP2 density. N-WASP with extra lysines also bypassed the usual activation mechanisms (i.e., PI5K activation and PIP2 synthesis) required for vesicle motility in vivo. Says Lim, "this implies that the native protein threshold is set just above the native density ," which is several-fold higher than that of other phospholipids. "It's tuned to optimize sensitivity," he says, "but also suppress noise under basal conditions."2 B, M1 J7 k  z; S

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Papayannopoulos, V., et al. 2005. Mol. Cell. 17:181–191.(Actin tails are induced by N-WASP (left))

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发表于 2025-5-31 23:27 |只看该作者
貌似我真的很笨????哎  

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发表于 2025-4-25 11:39 |只看该作者
勤奋真能造就财富吗?  

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发表于 2025-3-16 05:40 |只看该作者
干细胞之家微信公众号
活着,以死的姿态……  

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发表于 2025-3-5 10:30 |只看该作者
HOHO~~~~~~  

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发表于 2025-2-14 04:09 |只看该作者
我在努力中  

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发表于 2025-2-3 00:31 |只看该作者
不错不错.,..我喜欢  

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发表于 2025-1-26 13:09 |只看该作者
干细胞治疗糖尿病  

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发表于 2025-1-24 20:17 |只看该作者
发贴看看自己积分  

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发表于 2025-1-6 01:50 |只看该作者
加油啊!偶一定会追随你左右,偶坚定此贴必然会起到抛砖引玉的作用~  
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