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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,
