Ca2+ signals:
Molecular Mechanisms and Integrative Functions Collaborative Research Center 894

Project A2 - Barbara Niemeyer

Mechanisms and regulation of Ca2+ signals in immune cells by STIM and Orai proteins

Amplitude, duration and kinetics of Ca2+ signals code for changes in gene expression, degranulation, cytokine release, proliferation and migration in immune cells. These diverse functions require tight control of Ca2+ influx. We have analyzed the major influx pathway in immune cells, the CRAC (Ca2+ Release-Activated Ca2+) channels encoded by the Orai genes (Orai1-3) which are activated by ER localized STIM (STIM1 and STIM2) proteins. Unclear is how these components work together to produce such diverse Ca2+ profiles and how malfunctions affect the cellular fate, however, loss-of- or gain-of-function mutations of STIM or Orai lead to a number of pathologies.  

To understand the molecular composition and regulation of this Ca2+ influx pathway, we are studying regulation of STIM and Orai proteins by posttranslational modifications (glycosylation, phosphorylation), the influence of other and new regulatory proteins and differential channel composition by regulated expression of homologs and splice variants of the major players. During the current funding period, our main focus is to analyze the physiological role of a novel STIM2 splice variant. 

 

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Co-project leader Christine Peinelt has accepted the offer the University of Bern and has left the SFB 894 on June 30, 2016.