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

TitleAltering integrin engagement regulates membrane localization of Kir2.1 channels.
Publication TypeJournal Article
Year of Publication2019
AuthorsS Sengupta, KE Rothenberg, H Li, BD Hoffman, and N Bursac
JournalJournal of Cell Science
Volume132
Start Pagejcs225383
Issue17
Date Published09/2019
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 (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.

DOI10.1242/jcs.225383
Short TitleJournal of Cell Science