Adhesive receptors of the integrin family are primarily involved in cell-extracellular matrix adhesion. Additionally, integrins trigger multiple signaling pathways that are involved in cell migration, proliferation, survival, and differentiation. We previously demonstrated that the activation of integrins containing the β<sub>1</sub>, subunit leads to a selective increase in potassium currents carried by the human ether-a-go-go-related gene (hERG) channels in neuroblastoma and leukemia cells; this current activation modulates adhesion-dependent differentiation in these cells. We hypothesized that the cross-talk between integrins and hERG channels could be traced back to the assembly of a macromolecular signaling complex comprising the two proteins. We tested this hypothesis in both SH-SY5Y neuroblastoma cells and in human embryonic kidney 293 cells stably transfected with hERG1 and, therefore, expressing only the full-length hERG1 protein on the plasma membrane. The β<sub>1</sub> integrin and hERG1 coprecipitate in these cells and colocalize in both intracellular and surface membrane compartments. The two proteins also coprecipitate with caveolin-1, suggesting the localization of the complex in lipid rafts/caveolae. hERG1-transfected cells undergo an activation of hERG currents after β<sub>1</sub> integrin-mediated adhesion to fibronectin; concomitant with this activation, the focal adhesion kinase associates with the hERG1 protein and becomes tyrosine phosphorylated. Using hERG1-specific inhibitors, we show that the tyrosine phosphorylation of focal adhesion kinase is strictly dependent on hERG channel activity. Similarly, the activity of the small GTPase Rac1 turned out to be dependent on hERG currents. On the whole, these data indicate that the hERG1 protein associates with β<sub>1</sub> integrins and modulates adhesion receptor signaling. © 2005 by The American Society for Cell Biology.

Cherubini, A., Hofmann, G., Pillozzi, S., Guasti, L., Crociani, O., Cilia, E., et al. (2005). Human ether-à-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling. MOLECULAR BIOLOGY OF THE CELL, 16(6), 2972-2983 [10.1091/mbc.E04-10-0940].

Human ether-à-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling

WANKE, ENZO;BECCHETTI, ANDREA;
2005

Abstract

Adhesive receptors of the integrin family are primarily involved in cell-extracellular matrix adhesion. Additionally, integrins trigger multiple signaling pathways that are involved in cell migration, proliferation, survival, and differentiation. We previously demonstrated that the activation of integrins containing the β1, subunit leads to a selective increase in potassium currents carried by the human ether-a-go-go-related gene (hERG) channels in neuroblastoma and leukemia cells; this current activation modulates adhesion-dependent differentiation in these cells. We hypothesized that the cross-talk between integrins and hERG channels could be traced back to the assembly of a macromolecular signaling complex comprising the two proteins. We tested this hypothesis in both SH-SY5Y neuroblastoma cells and in human embryonic kidney 293 cells stably transfected with hERG1 and, therefore, expressing only the full-length hERG1 protein on the plasma membrane. The β1 integrin and hERG1 coprecipitate in these cells and colocalize in both intracellular and surface membrane compartments. The two proteins also coprecipitate with caveolin-1, suggesting the localization of the complex in lipid rafts/caveolae. hERG1-transfected cells undergo an activation of hERG currents after β1 integrin-mediated adhesion to fibronectin; concomitant with this activation, the focal adhesion kinase associates with the hERG1 protein and becomes tyrosine phosphorylated. Using hERG1-specific inhibitors, we show that the tyrosine phosphorylation of focal adhesion kinase is strictly dependent on hERG channel activity. Similarly, the activity of the small GTPase Rac1 turned out to be dependent on hERG currents. On the whole, these data indicate that the hERG1 protein associates with β1 integrins and modulates adhesion receptor signaling. © 2005 by The American Society for Cell Biology.
Articolo in rivista - Articolo scientifico
ERG, K+ channels, SH-SY5Y, Rac1, focal adhesion kinase, FAK, HEK, caveolin-1, raft, tyrosine phosphorylation
English
2005
16
6
2972
2983
none
Cherubini, A., Hofmann, G., Pillozzi, S., Guasti, L., Crociani, O., Cilia, E., et al. (2005). Human ether-à-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling. MOLECULAR BIOLOGY OF THE CELL, 16(6), 2972-2983 [10.1091/mbc.E04-10-0940].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/1007
Citazioni
  • Scopus 146
  • ???jsp.display-item.citation.isi??? 134
Social impact