The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K+ release from necrotic cells and hypoxia affecting the expression of K+ channels. The groups of György Vámosi and György Panyi: Éva Nagy, Gábor Mocsár, Veronika Sebestyén, Julianna Volkó and Ferenc Papp, in collaboration with Thomas Waldmann (USA) and Katalin Tóth (Germany) studied the influence of membrane de- and hyperpolarization on the biophysical properties and signaling of interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors, which play important roles in T cell function. Depolarization and hyperpolarization caused a change of mobility in the mobility of these receptors, and the effect correlated with the charge distribution of these proteins near the plasma membrane. MP changes modulated signaling by the two cytokines in distinct ways: depolarization caused a significant increase in the IL-2-induced phosphorylation of STAT 5, whereas hyperpolarization evoked a decrease only in the IL-15-induced signal. Our data imply that the MP may be an important modulator of interleukin receptor signaling and dynamics. Enhanced IL-2 signaling in depolarized Treg cells highly expressing IL-2R may contribute to suppression of antitumor immune surveillance.
(Nagy É et al. Biophys J. 2018 May 22;114(10):2473-2482.)