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Printable Handouts
Navigable Slide Index
- Introduction
- STIM and Orai
- STIM & Orai in resting T cells
- STIM & Orai in activated T cells
- Store independent calcium entry
- Icrac and Iarc
- Summary of the first part
- STIM1, immunodeficiency and cancer
- STIM1 structure
- Luminal calcium depletion
- STIM1 mutants
- STIM1 mutations and immunodeficiency
- STIM1 mutation: E128RfsX9 / E136X
- STIM1 mutation: 1538-1G>A
- Severe primary immunodeficiencies
- R429C mutation in STIM
- Mutations in STIM1 and cancer (1)
- Mutations in STIM1 and cancer (2)
- STIM2 structure
- The role of STIM2 in SOCE
- STIM2 overexpression and SOCE
- STIM2 and calcium
- STIM2 and cancer
- Orai1, immunodeficiency and cancer
- Orai1 sequence
- Orai1 structure
- Important domains for STIM1 and Orai1 interaction
- Orai1 mutations and immunodeficiency
- Orai1 A88SfsX25
- Missense mutations in Orai1
- Orai1 and CRAC channels
- Diseases associated with Orai1
- Orai1 mutation E106Q
- Mutations in Orai1 and cancer
- Orai2 sequence
- Mutations in Orai2 and cancer
- Orai3 sequence
- Orai3, SOCE & Icrac in MCF7 breast cancer cells
- Mutations in Orai3 and cancer
- E81Q-Orai3 mutation
- Conclusion and perspectives
- Summary
- Short list of reviews
- Acknowledgements
Topics Covered
- STIM/Orai
- two major molecular components of the calcium entry pathways observed in all tissues and associated to several physiological functions
- Mutations causing immunodeficiencies and cancer by altering calcium homeostasis.
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Talk Citation
Capiod, T. (2012, October 31). Immunodeficiencies and pathologies associated with mutations in STIM/ORAI [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/KHDX7292.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Thierry Capiod has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
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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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