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Altering integrin engagement regulates membrane localization of Kir2.1 channels.
Sengupta, Swarnali; Rothenberg, Katheryn E; Li, Hanjun; Hoffman, Brenton D; Bursac, Nenad.
Afiliação
  • Sengupta S; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
  • Rothenberg KE; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
  • Li H; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
  • Hoffman BD; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA nbursac@duke.edu brenton.hoffman@duke.edu.
  • Bursac N; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA nbursac@duke.edu brenton.hoffman@duke.edu.
J Cell Sci ; 132(17)2019 09 02.
Article em En | MEDLINE | ID: mdl-31391240
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Integrinas / Ativação do Canal Iônico / Canais de Potássio Corretores do Fluxo de Internalização / Potenciais da Membrana Limite: Animals / Female / Humans Idioma: En Revista: J Cell Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Integrinas / Ativação do Canal Iônico / Canais de Potássio Corretores do Fluxo de Internalização / Potenciais da Membrana Limite: Animals / Female / Humans Idioma: En Revista: J Cell Sci Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos