Phosphoinositides alter lipid bilayer properties.
Phosphoinositides alter lipid bilayer properties.
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DOI：
10.1085/jgp.201310960
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Andersen OS
中科院分区：
文献类型：
--
作者：
Rusinova R;Hobart EA;Koeppe RE 2nd;Andersen OS
磷脂酰肌醇 - 4,5 - 二磷酸（PIP2）约占质膜磷脂的1%，在膜限定的信号传导中起关键作用。PIP2调节结构和功能多样的膜蛋白，包括电压门控和配体门控离子通道、内向整流离子通道、转运蛋白和受体。在某些情况下，已知这种调节涉及特定的脂质 - 蛋白质相互作用，但PIP2调节其众多不同靶点的机制仍有待完全阐明。由于许多PIP2靶点是跨膜蛋白，我们探究了磷酸肌醇是否可能改变双层物理性质，如曲率和弹性，这将改变膜蛋白构象状态之间的平衡，进而改变蛋白质功能。利用短杆菌肽A（gA）通道对脂质双层性质变化的敏感性，我们使用基于gA的荧光猝灭和单通道测定法来检测长链PIP2（脑PIP2，主要是1 - 硬脂酰 - 2 - 花生四烯酰 - PIP2，以及二油酰 - PIP2）对双层性质的影响。当以2摩尔%与二油酰 - 磷脂胆碱预混合时，两种长链PIP2在gA通道功能（双层性质）方面产生相似的变化；然而，当通过水溶液施加时，脑PIP2是比二油酰 - PIP2更有效的调节剂。鉴于短链二辛酰 - 磷酸肌醇的广泛使用，我们还检测了二C8 - 磷酸肌醇（PI）、PI(4,5)P2、PI(3,5)P2、PI(3,4)P2和PI(3,4,5)P3的影响。除PI(3,5)P2外，二C8磷酸肌醇改变双层性质的效力随着头部基团电荷的增加而降低。非磷酸肌醇二C8磷脂通常是比多磷酸肌醇更有效的双层调节剂。这些结果表明，由于PI激酶或磷酸酶的激活，质膜PIP2水平的生理性增加或降低除了可能产生的任何其他影响外，还可能改变脂质双层性质。结果进一步表明，外源性PIP2以及在酰基链长度或磷酸化状态上不同的结构类似物，在许多细胞生理学实验所使用的浓度下会改变脂质双层性质。
Phosphatidylinositol-4,5-bisphosphate (PIP2), which constitutes ∼1% of the plasma membrane phospholipid, plays a key role in membrane-delimited signaling. PIP2 regulates structurally and functionally diverse membrane proteins, including voltage- and ligand-gated ion channels, inwardly rectifying ion channels, transporters, and receptors. In some cases, the regulation is known to involve specific lipid–protein interactions, but the mechanisms by which PIP2 regulates many of its various targets remain to be fully elucidated. Because many PIP2 targets are membrane-spanning proteins, we explored whether the phosphoinositides might alter bilayer physical properties such as curvature and elasticity, which would alter the equilibrium between membrane protein conformational states—and thereby protein function. Taking advantage of the gramicidin A (gA) channels’ sensitivity to changes in lipid bilayer properties, we used gA-based fluorescence quenching and single-channel assays to examine the effects of long-chain PIP2s (brain PIP2, which is predominantly 1-stearyl-2-arachidonyl-PIP2, and dioleoyl-PIP2) on bilayer properties. When premixed with dioleoyl-phosphocholine at 2 mol %, both long-chain PIP2s produced similar changes in gA channel function (bilayer properties); when applied through the aqueous solution, however, brain PIP2 was a more potent modifier than dioleoyl-PIP2. Given the widespread use of short-chain dioctanoyl-phosphoinositides, we also examined the effects of diC8-phosphoinositol (PI), PI(4,5)P2, PI(3,5)P2, PI(3,4)P2, and PI(3,4,5)P3. The diC8 phosphoinositides, except for PI(3,5)P2, altered bilayer properties with potencies that decreased with increasing head group charge. Nonphosphoinositide diC8 phospholipids generally were more potent bilayer modifiers than the polyphosphoinositides. These results show that physiological increases or decreases in plasma membrane PIP2 levels, as a result of activation of PI kinases or phosphatases, are likely to alter lipid bilayer properties, in addition to any other effects they may have. The results further show that exogenous PIP2, as well as structural analogues that differ in acyl chain length or phosphorylation state, alters lipid bilayer properties at the concentrations used in many cell physiological experiments.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
3.6
作者：
Artigas, Pablo;Al'Aref, Subhi J.;Andersen, Olaf S.
通讯作者：
Andersen, Olaf S.
DOI：
10.1126/stke.2002.125.pl3
发表时间：
2002-03-26
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Balla, Tamas;Varnai, Peter
通讯作者：
Varnai, Peter
DOI：
10.1016/0005-2736(86)90015-5
发表时间：
1986-03-27
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BULLOCK, JO;COHEN, FS
通讯作者：
COHEN, FS
DOI：
10.1051/jp2:1994227
发表时间：
1994-10-01
期刊：
JOURNAL DE PHYSIQUE II
影响因子：
--
作者：
DAN, N;BERMAN, A;SAFRAN, SA
通讯作者：
SAFRAN, SA