Journal article
Altering integrin engagement regulates membrane localization of K(ir)2.1 channels
Journal of cell science, Vol.132(17), 225383
09/01/2019
DOI: 10.1242/jcs.225383
PMCID: PMC6771140
PMID: 31391240
Abstract
How ion channels localize and distribute on the cell membrane remains incompletely understood. We show that interventions that vary cell adhesion proteins and cell size also affect the membrane current density of inward-rectifier K+ channels (K(ir)2.1; encoded by KCNJ2) and profoundly alter the action potential shape of excitable cells. By using micropatterning to manipulate the localization and size of focal adhesions (FAs) in single HEK293 cells engineered to stably express K(ir)2.1 channels or in neonatal rat cardiomyocytes, we establish a robust linear correlation between FA coverage and the amplitude of K(ir)2.1 current at both the local and whole-cell levels. Confocal microscopy showed that Ki r 2.1 channels accumulate in membrane proximal to FAs. Selective pharmacological inhibition of key mediators of protein trafficking and the spatially dependent alterations in the dynamics of K(ir)2.1 fluorescent recovery after photobleaching revealed that the K(ir)2.1 channels are transported to the cell membrane uniformly, but are preferentially internalized by endocytosis at sites that are distal from FAs. Based on these results, we propose adhesion-regulated membrane localization of ion channels as a fundamental mechanism of controlling cellular electrophysiology via mechanochemical signals, independent of the direct ion channel mechanogating.
Details
- Title: Subtitle
- Altering integrin engagement regulates membrane localization of K(ir)2.1 channels
- Creators
- Swarnali Sengupta - Duke UniversityKatheryn E. Rothenberg - Duke UniversityHanjun Li - Duke UniversityBrenton D. Hoffman - Duke UniversityNenad Bursac - Duke University
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.132(17), 225383
- Publisher
- Company Biologists Ltd
- DOI
- 10.1242/jcs.225383
- PMID
- 31391240
- PMCID
- PMC6771140
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Number of pages
- 16
- Grant note
- National Science Foundation; National Science Foundation (NSF) R01HL132389 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 1R01HL126524; 1R01HL132389; U01HL134764 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/01/2019
- Academic Unit
- Biology
- Record Identifier
- 9984696709702771
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