Differential targeting of shaker-like potassium channels to lipid rafts
Differential targeting of shaker-like potassium channels to lipid rafts
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DOI：
10.1074/jbc.275.11.7443
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发表时间：
2000-03-17
影响因子：
4.8
通讯作者：
Tamkun, MM
中科院分区：
文献类型：
--
作者：
Martens, JR;Navarro-Polanco, R;Tamkun, MM
神经元和肌肉细胞膜内的离子通道靶向是电兴奋性的一个重要决定因素。最近的证据表明，在细胞膜内存在着通常被称为脂筏的特殊微区。这些结构域富含胆固醇和鞘脂，并集中了许多信号转导蛋白，如一氧化氮合酶，配体门控受体，和多种蛋白激酶，在这里，我们证明，电压门控K+通道Kv2.1，但不是Kv4.2，目标脂筏在异源表达SG系统和大鼠脑。Kv2.1与脂筏的关联似乎不涉及小窝蛋白。细胞胆固醇的耗尽改变了Kv2.1相关筏的浮力，并将Kv2.1失活的中点移动了近40 mV，而不影响峰值电流密度或通道激活。K+通道对脂筏的差异靶向代表了一种新的机制，既用于将K+通道亚细胞分选到富含信号复合物的膜区域，又用于通过脂质含量的改变来调节通道特性。
Ion channel targeting within neuronal and muscle membranes is an important determinant of electrical excitability, Recent evidence suggests that there exists within the membrane specialized microdomains commonly referred to as lipid rafts. These domains are enriched in cholesterol and sphingolipids and concentrate a number of signal transduction proteins such as nitric-oxide synthase, ligand-gated receptors, and multiple protein kinases, Here, we demonstrate that the voltage-gated K+ channel Kv2.1, but not Kv4.2, targets to lipid rafts in both heterologous expression sg systems and rat brain. The Kv2.1 association with lipid rafts does not appear to involve caveolin. Depletion of cellular cholesterol alters the buoyancy of the Kv2.1 associated rafts and shifts the midpoint of Kv2.1 inactivation by nearly 40 mV without affecting peak current density or channel activation. The differential targeting of K+ channels to lipid rafts represents a novel mechanism both for the subcellular sorting of K+ channels to regions of the membrane rich in signaling complexes and for modulating channel properties via alterations in lipid content.