Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D.

Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D.
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DOI:
10.1038/ncomms13873
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发表时间:
2016-12-15
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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对物理力量的感知,即机械感觉,是人类五种感官中的两种--触觉和听觉的基础。膜中的力是如何传递的,目前还不清楚。我们问生物膜是否可以利用动能在没有张力的情况下传递信号。在这里,我们表明,脂筏是一个动态的隔室,它通过将磷脂酶D2(PLD2)从底物中隔离出来,使其失活。脂筏的机械破坏通过将酶与其底物混合来激活PLD2,从而产生信号转导的脂质磷脂酸(PA)。我们计算了混频激活PLD的潜伏期为<650 μS。我们的结果建立了一种快速、无张力的机械转导机制,其中有序脂类的破坏通过机械混合启动了细胞生长的机械敏感信号。生物膜的机械传感可以通过对离子通道的机械张力来传递。作者证明了磷脂酶D(PLD)是通过脂筏的机械破坏而被激活的,从而使PLD与其在脂膜中的底物混合,并提出了一个力传递的动力学模型。
The sensing of physical force, mechanosensation, underlies two of five human senses—touch and hearing. How transduction of force in a membrane occurs remains unclear. We asked if a biological membrane could employ kinetic energy to transduce a signal absent tension. Here we show that lipid rafts are dynamic compartments that inactivate the signalling enzyme phospholipase D2 (PLD2) by sequestering the enzyme from its substrate. Mechanical disruption of the lipid rafts activates PLD2 by mixing the enzyme with its substrate to produce the signalling lipid phosphatidic acid (PA). We calculate a latency time of <650 μs for PLD activation by mixing. Our results establish a fast, non-tension mechanism for mechanotransduction where disruption of ordered lipids initiates a mechanosensitive signal for cell growth through mechanical mixing. Mechanosensation by biological membranes can be relayed by mechanical tension to ion channels. Here the authors show that phospholipase D (PLD) is activated by mechanical disruption of lipid rafts which allows PLD to mix with its substrate in the lipid membrane, and propose a kinetic model of force transduction.
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