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

Autor: Anees P; Department of Chemistry, The University of Chicago, Chicago, IL, USA.; Grossman Center for Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL, USA.; Institute of Biophysical Dynamics, The University of Chicago, Chicago, IL, USA., Saminathan A; Department of Chemistry, The University of Chicago, Chicago, IL, USA.; Grossman Center for Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL, USA., Rozmus ER; Department of Physiology, University of Kentucky College of Medicine, Lexington, KY, USA., Di A; Department of Pharmacology and Regenerative Medicine, The University of Illinois College of Medicine, Chicago, IL, USA., Malik AB; Department of Pharmacology and Regenerative Medicine, The University of Illinois College of Medicine, Chicago, IL, USA., Delisle BP; Department of Physiology, University of Kentucky College of Medicine, Lexington, KY, USA. brian.delisle@uky.edu., Krishnan Y; Department of Chemistry, The University of Chicago, Chicago, IL, USA. yamuna@uchicago.edu.; Grossman Center for Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL, USA. yamuna@uchicago.edu.; Institute of Biophysical Dynamics, The University of Chicago, Chicago, IL, USA. yamuna@uchicago.edu.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2024 Jul; Vol. 42 (7), pp. 1065-1074. Date of Electronic Publication: 2023 Sep 21.
DOI: 10.1038/s41587-023-01928-z
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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