美国芝加哥大学Yamuna Krishnan和肯塔基大学医学院Brian P. Delisle团队合作的最新研究，利用DNA纳米元件揭示了细胞器特异性钾离子（K^₊）通道活性。这一研究成果于2023年9月21日发表在国际学术期刊《自然-生物技术》上。

研究人员揭示了一种名为pHlicKer的pH可校正K^₊比率报告基因，使用它来探测原型电压门控K^₊通道Kv11.1的区室特异性活性，并表明该细胞表面通道在细胞器中是活跃的。细胞器中的管腔K^₊在表达野生型Kv11.1通道的细胞中增加，但在用电流阻断剂处理后增加消失。转运功能受损的Kv11.1突变通道未能增加回收内体中的K^₊水平，这种效应可通过药物挽救。

通过提供一种绘制K+通道细胞器特异性活性的方法，pHlicKer技术可以帮助识别新的细胞器K^₊通道或具有功能的通道调节剂。

研究人员表示，细胞表面钾离子通道通过控制K^₊通透性来调节营养物质运输、细胞迁移和细胞间通讯，并且一般认为钾离子通道仅在质膜处具有活性。尽管这些通道在反式高尔基体网络、早期和循环的内吞体中分布，但尚不清楚它们在这些细胞器中是否活跃。

附：英文原文

Title: Detecting organelle-specific activity of potassium channels with a DNA nanodevice

Author: Anees, Palapuravan, Saminathan, Anand, Rozmus, Ezekiel R., Di, Anke, Malik, Asrar B., Delisle, Brian P., Krishnan, Yamuna

Issue&Volume: 2023-09-21

Abstract: Cell surface potassium ion (K+) channels regulate nutrient transport, cell migration and intercellular communication by controlling K+ permeability and are thought to be active only at the plasma membrane. Although these channels transit the trans-Golgi network, early and recycling endosomes, whether they are active in these organelles is unknown. Here we describe a pH-correctable, ratiometric reporter for K+ called pHlicKer, use it to probe the compartment-specific activity of a prototypical voltage-gated K+ channel, Kv11.1, and show that this cell surface channel is active in organelles. Lumenal K+ in organelles increased in cells expressing wild-type Kv11.1 channels but not after treatment with current blockers. Mutant Kv11.1 channels, with impaired transport function, failed to increase K+ levels in recycling endosomes, an effect rescued by pharmacological correction. By providing a way to map the organelle-specific activity of K+ channels, pHlicKer technology could help identify new organellar K+ channels or channel modulators with nuanced functions.

DOI: 10.1038/s41587-023-01928-z

Source: https://www.nature.com/articles/s41587-023-01928-z