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001-es BibID:	BIBFORM075364
035-os BibID:	(WoS)000432700300024 (Scopus)85046862526
Első szerző:	Nagy Éva (molekuláris biológus)
Cím:	Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells / Éva Nagy, Gábor Mocsár, Veronika Sebestyén, Julianna Volkó, Ferenc Papp, Katalin Tóth, Sándor Damjanovich, György Panyi, Thomas A. Waldmann, Andrea Bodnár, György Vámosi
Dátum:	2018
ISSN:	0006-3495
Megjegyzések:	The high electric ?eld across the plasma membrane might in?uence 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 in?amed tissues because of K ? release from necrotic cells and hypoxia affecting the expression of K ? channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function. Therefore, we studied the in?uence 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. We investigated the mobility, clustering, and signaling of these receptors and major histocompatibility complex (MHC) I/II glycoproteins forming coclusters in lipid rafts of T cells. Depolarization by high K ? buffer or K channel blockers resulted in a decrease in the mobility of IL-2Ra and MHC glycoproteins, as shown by ?uorescence correlation spectroscopy, whereas hyperpolarization by the K ? ionophore valinomycin increased their mobility. Contrary to this, the mobility of IL-15Ra decreased upon both de- and hyperpolarization. These changes in protein mobility are not due to an alteration of membrane ?uidity, as evidenced by ?uorescence anisotropy measurements. Fo ? rster resonance energy transfer measurements showed that most homo- or heteroassociations of IL-2R, IL-15R, and MHC I did not change considerably, either. MP changes modulated signaling by the two cytokines in distinct ways: depolarization caused a signi?cant increase in the IL-2-induced phosphorylation of signal transducer and activator of transcription 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 T reg ? cells highly expressing IL-2R may contribute to suppression of antitumor immune surveillance
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Biophysical Journal. - 114 : 10 (2018), p. 2473-2482. -
További szerzők:	Mocsár Gábor (1981-) (biofizikus) Borbásné Sebestyén Veronika (1990-) (biofizikus) Volkó Julianna (1983-) (biotechnológus) Papp Ferenc (1979-) (biofizikus) Tóth Katalin (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus) Panyi György (1966-) (biofizikus) Waldmann, Thomas A. Dóczy-Bodnár Andrea (1970-) (biofizikus) Vámosi György (1967-) (biofizikus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00026 GINOP GINOP-2.3.3-15-2016-00003 GINOP GINOP-2.3.3-15-2016-00030 GINOP K103965 OTKA EFOP-3.6.1-16-2016-00022 EFOP K119417 OTKA TÁMOP-4.2.4.A/2-11/1-2012-0001 TÁMOP EFOP-3.6.3-VEKOP-16-2017-00009 EFOP
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