Redox regulation of leukocyte calcium signaling and function

• Antragstellerinnen / Antragsteller: Professor Dr. Ivan Bogeski; Professorin Barbara Anne Niemeyer, Ph.D.
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2011 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 204981740

T cell activation, differentiation and proliferation critically depends on the store-operated Ca2+-entry (SOCE) mediated by Orai ion channels. Within inflamed tissues, T cells are exposed to reactive oxy-gen species (ROS) produced by activated phagocytes. In our recent study we have examined the interplay between ROS and Orai channels and found that oxidation inhibits SOCE. This inhibition is mediated through oxidation of a specific cysteine present in Orai1 and 2 and absent in Orai3 channels. However, the exact molecular mechanisms of Orai inhibition by H2O2 and of Orai-independent effects of ROS are not well understood. Utilizing various techniques we will address whether and how oxidation affects the mechanism of Orai channel inhibition, how and which non-selective cation channels are activated in T cells and whether upregulation of the redox-insensitive Orai3 is relevant for the physiological function of activated ROS producing phagocytes. The long term perspective aims at understanding the impact of ROS regulation and dysregulation of Ca2+ signalling under normal and pathological conditions.

• DFG-Verfahren: Sachbeihilfen