The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels.
The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels.
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DOI：
10.1523/jneurosci.5978-08.2009
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发表时间：
2009-04-29
期刊：
影响因子：
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通讯作者：
Kaczmarek LK
中科院分区：
文献类型：
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作者：
Chen H;Kronengold J;Yan Y;Gazula VR;Brown MR;Ma L;Ferreira G;Yang Y;Bhattacharjee A;Sigworth FJ;Salkoff L;Kaczmarek LK
细胞内Na+离子激活的钾通道在调节神经元放电模式中起着多种不同的作用，并且在单通道水平上，它们的特性是相当多样的。两个已知的基因，Slick和Slack，编码KNa通道。我们现在已经发现，Slick和Slack亚基共组装形成异聚体通道，异聚体通道在其单一电导、动力学行为、亚细胞定位和对蛋白激酶C活化的响应方面不同于同聚体。异源聚体的形成需要Slack-B的N-末端结构域，Slack通道的两个可变剪接变体之一。该Slack-B的细胞质N-末端结构域还促进异聚KNa通道定位于质膜。免疫细胞化学研究表明，Slick和Slack-B亚基在许多中枢神经元中共表达。我们的研究结果提供了一个分子解释的一些多样性，在报告的性质神经元KNa通道。
Potassium channels activated by intracellular Na+ ions (KNa) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, Slick and Slack, encode KNa channels. We have now found that Slick and Slack subunits co-assemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization and their response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of two alternative splice variants the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric KNa channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are co-expressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal KNa channels.