course: The spatio-temporal calcium signature in STIM-Orai microdomains
speaker: Rüdinger Thul (University of Nottingham)abstract: In many cell types, calcium (Ca2+) is released from intracellular storage compartments such as the endoplasmic reticulum (ER) to generate distinct Ca2+ patterns including Ca2+ oscillations. To replenish the ER once luminal Ca2+ levels have dropped, cells employ a process called store-operated Ca2+ entry, which coordinates Ca2+ influx across the plasma membrane (PM). This influx pathway is controlled by two main molecular components, Orai channels and STIM molecules, which reside in small ER-PM junctions. These so-called STIM-Orai microdomains are crucial for driving endothelial cell proliferation and oocyte maturation, to name but a few. I will present a recently developed three-dimensional model of a STIM-Orai microdomain and discuss crucial aspects of the model development. We used the model to investigate the role of Orai channel and SERCA pump placement in refilling of the ER. We found that the organisation of Orai channels within the ER-PM junction controls the amplitude and shape of the Ca2+ profile but does not enhance ER refilling. Testing different SERCA pump isoforms, we saw that the positions of SERCA2a pumps control refilling to a greater extent than those of SERCA2b pumps.
timetable:
Tue 9 Oct, 11:00 - 12:00, Aula Dini
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