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Altering integrin engagement regulates membrane localization of Kir2.1 channels.

Publication ,  Journal Article
Sengupta, S; Rothenberg, KE; Li, H; Hoffman, BD; Bursac, N
Published in: Journal of cell science
September 2019

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 (Kir2.1; 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 Kir2.1 channels or in neonatal rat cardiomyocytes, we establish a robust linear correlation between FA coverage and the amplitude of Kir2.1 current at both the local and whole-cell levels. Confocal microscopy showed that Kir2.1 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 Kir2.1 fluorescent recovery after photobleaching revealed that the Kir2.1 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.

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Published In

Journal of cell science

DOI

EISSN

1477-9137

ISSN

0021-9533

Publication Date

September 2019

Volume

132

Issue

17

Start / End Page

jcs225383

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Potassium Channels, Inwardly Rectifying
  • Membrane Potentials
  • Ion Channel Gating
  • Integrins
  • Humans
  • HEK293 Cells
  • Female
  • Endocytosis
 

Citation

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Sengupta, S., Rothenberg, K. E., Li, H., Hoffman, B. D., & Bursac, N. (2019). Altering integrin engagement regulates membrane localization of Kir2.1 channels. Journal of Cell Science, 132(17), jcs225383. https://doi.org/10.1242/jcs.225383
Sengupta, Swarnali, Katheryn E. Rothenberg, Hanjun Li, Brenton D. Hoffman, and Nenad Bursac. “Altering integrin engagement regulates membrane localization of Kir2.1 channels.Journal of Cell Science 132, no. 17 (September 2019): jcs225383. https://doi.org/10.1242/jcs.225383.
Sengupta S, Rothenberg KE, Li H, Hoffman BD, Bursac N. Altering integrin engagement regulates membrane localization of Kir2.1 channels. Journal of cell science. 2019 Sep;132(17):jcs225383.
Sengupta, Swarnali, et al. “Altering integrin engagement regulates membrane localization of Kir2.1 channels.Journal of Cell Science, vol. 132, no. 17, Sept. 2019, p. jcs225383. Epmc, doi:10.1242/jcs.225383.
Sengupta S, Rothenberg KE, Li H, Hoffman BD, Bursac N. Altering integrin engagement regulates membrane localization of Kir2.1 channels. Journal of cell science. 2019 Sep;132(17):jcs225383.
Journal cover image

Published In

Journal of cell science

DOI

EISSN

1477-9137

ISSN

0021-9533

Publication Date

September 2019

Volume

132

Issue

17

Start / End Page

jcs225383

Related Subject Headings

  • Rats, Sprague-Dawley
  • Rats
  • Potassium Channels, Inwardly Rectifying
  • Membrane Potentials
  • Ion Channel Gating
  • Integrins
  • Humans
  • HEK293 Cells
  • Female
  • Endocytosis