Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7.
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Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7. / Adriouch, Sahil; Scheuplein, Felix; Bähring, Robert; Seman, Michel; Boyer, Olivier; Koch Nolte, Friedrich; Haag, Friedrich.
in: PURINERG SIGNAL, Jahrgang 5, Nr. 2, 2, 2009, S. 151-161.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7.
AU - Adriouch, Sahil
AU - Scheuplein, Felix
AU - Bähring, Robert
AU - Seman, Michel
AU - Boyer, Olivier
AU - Koch Nolte, Friedrich
AU - Haag, Friedrich
PY - 2009
Y1 - 2009
N2 - The cytolytic P2X7 purinoceptor is widely expressed on leukocytes and has sparked interest because of its key role in the activation of the inflammasome, the release of the pro-inflammatory cytokine IL-1beta and cell death. We report here the functional characterisation of a R276A gain-of-function mutant analysed for its capacities to induce membrane depolarisation, calcium influx and opening of a large membrane pore permeable to YO-PRO-1. Our results highlight the particular sensitivity of R276A mutant to low micromolar adenosine triphosphate (ATP) concentrations, which possibly reflect an increased affinity for its ligands, and a slower closing kinetics of the receptor channel. Our findings support the notion that evolutionary pressures maintain the low sensitivity of P2X7 to ATP. We also believe that the R276A mutant described here may be useful for the generation of new animal models with exacerbated P2X7 functions that will serve to better characterise its role in inflammation and in immune responses.
AB - The cytolytic P2X7 purinoceptor is widely expressed on leukocytes and has sparked interest because of its key role in the activation of the inflammasome, the release of the pro-inflammatory cytokine IL-1beta and cell death. We report here the functional characterisation of a R276A gain-of-function mutant analysed for its capacities to induce membrane depolarisation, calcium influx and opening of a large membrane pore permeable to YO-PRO-1. Our results highlight the particular sensitivity of R276A mutant to low micromolar adenosine triphosphate (ATP) concentrations, which possibly reflect an increased affinity for its ligands, and a slower closing kinetics of the receptor channel. Our findings support the notion that evolutionary pressures maintain the low sensitivity of P2X7 to ATP. We also believe that the R276A mutant described here may be useful for the generation of new animal models with exacerbated P2X7 functions that will serve to better characterise its role in inflammation and in immune responses.
M3 - SCORING: Zeitschriftenaufsatz
VL - 5
SP - 151
EP - 161
JO - PURINERG SIGNAL
JF - PURINERG SIGNAL
SN - 1573-9538
IS - 2
M1 - 2
ER -
