Immunodeficiencies and pathologies associated with mutations in STIM/ORAI

Published on October 31, 2012   38 min

Other Talks in the Series: Calcium Signaling II

0:00
Hello. My name is Thierry Capiod, and I am leading a team at the Hospital Necker for Sick Children in Paris. I currently work on the role of calcium-signaling proteins in cell proliferation and cell growth. And in this talk, I shall review the consequences of known mutation in two families of proteins involved in calcium influx in immunodeficiency and other physiopathological diseases.
0:32
The two families are STIM for Stromal Interaction Molecule, and Orai. Two forms of STIM and three forms of Orai have been identified so far. Orai proteins are exclusively located in the plasma membrane. STIM1 and STIM2 are preferentially found on the endoplasmic reticulum membrane, but a small proportion of STIM1 is also found on the plasma membrane. Together, STIM and Orai form the main component of the store-operated calcium entry or SOCE. The calcium entry which takes its name from ER calcium stores depletion observed during cell activation.
1:26
The first example I should use to describe this model concerns T cells activation. STIM1 and STIM2 are transmembrane proteins that can directly breach the endoplasmic reticulum through the plasma membrane at specialized junctions. And the calcium-binding sites located on the intraluminal region of the proteins can sense the level of calcium within the ER that trigger the opening of calcium channels on the plasma membrane in response to an external stimulation. Calcium binds on two sites located on the intraluminal region of STIM with calcium affinities of about 200 micromolar and 400 micromolar for STIM1 and STIM2 respectively. In resting T cells, as ER calcium content is in the 500 micromolar range, STIM1 is kept inactive by binding of calcium to an EF-hand located in the ER middle part of STIM1. Activation of T cells via the TCR receptor leads to the production of IP3 which, in turn,
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Immunodeficiencies and pathologies associated with mutations in STIM/ORAI

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