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Open AccessArticle

Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation

1
Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile
2
Facultad de Ciencias, Instituto de Neurociencias and Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso 2381850, Chile
3
Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Av. República 330, Santiago 8370146, Chile
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9180; https://doi.org/10.3390/ijms21239180
Received: 15 November 2020 / Revised: 19 November 2020 / Accepted: 27 November 2020 / Published: 2 December 2020
Pannexin 1 channels located in the cell membrane are permeable to ions, metabolites, and signaling molecules. While the activity of these channels is known to be modulated by phosphorylation on T198, T308, and S206, the possible involvement of other putative phosphorylation sites remains unknown. Here, we describe that the activity of Panx1 channels induced by mechanical stretch is reduced by adenosine via a PKA-dependent pathway. The mechanical stretch-induced activity—measured by changes in DAPI uptake—of Panx1 channels expressed in HeLa cell transfectants was inhibited by adenosine or cAMP analogs that permeate the cell membrane. Moreover, inhibition of PKA but not PKC, p38 MAPK, Akt, or PKG prevented the effects of cAMP analogs, suggesting the involvement of Panx1 phosphorylation by PKA. Accordingly, alanine substitution of T302 or S328, two putative PKA phosphorylation sites, prevented the inhibitory effect of cAMP analogs. Moreover, phosphomimetic mutation of either T302 or S328 to aspartate prevented the mechanical stretch-induced activation of Panx1 channels. A molecular dynamics simulation revealed that T302 and S328 are located in the water–lipid interphase near the lateral tunnel of the intracellular region, suggesting that their phosphorylation could promote conformational changes in lateral tunnels. Thus, Panx1 phosphorylation via PKA could be modulated by G protein-coupled receptors associated with the Gs subunit. View Full-Text
Keywords: protein phosphorylation; site-directed mutation; dye uptake; adenosine; cAMP protein phosphorylation; site-directed mutation; dye uptake; adenosine; cAMP
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MDPI and ACS Style

López, X.; Escamilla, R.; Fernández, P.; Duarte, Y.; González-Nilo, F.; Palacios-Prado, N.; Martinez, A.D.; Sáez, J.C. Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation. Int. J. Mol. Sci. 2020, 21, 9180.

AMA Style

López X, Escamilla R, Fernández P, Duarte Y, González-Nilo F, Palacios-Prado N, Martinez AD, Sáez JC. Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation. International Journal of Molecular Sciences. 2020; 21(23):9180.

Chicago/Turabian Style

López, Ximena; Escamilla, Rosalba; Fernández, Paola; Duarte, Yorley; González-Nilo, Fernando; Palacios-Prado, Nicolás; Martinez, Agustín D.; Sáez, Juan C. 2020. "Stretch-Induced Activation of Pannexin 1 Channels Can Be Prevented by PKA-Dependent Phosphorylation" Int. J. Mol. Sci. 21, no. 23: 9180.

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