A minimal regulatory domain in the C terminus of STIM1 binds to and activates ORAI1 CRAC channels

Store-operated Ca 2+ entry (SOCE) is a universal mechanism to increase intracellular Ca 2+ concentrations in non-excitable cells. It is initiated by the depletion of ER Ca 2+ stores, activation of stromal interaction molecule (STIM) 1 and gating of the Ca 2+ release activated Ca 2+ (CRAC) channel OR...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-07, Vol.385 (1), p.49-54
Main Authors: Kawasaki, Takumi, Lange, Ingo, Feske, Stefan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Ca 2
Calcium
Calcium Channels - genetics
Calcium Channels - metabolism
CCb7
CCb9
Cell Line
CRAC
Humans
Membrane Proteins - genetics
Membrane Proteins - metabolism
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
ORAI1
ORAI1 Protein
Peptides - genetics
Peptides - metabolism
Protein Binding
Protein Structure, Tertiary
SOCE
STIM1
Store-operated calcium entry
Stromal interaction molecule
Stromal Interaction Molecule 1
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Summary:Store-operated Ca 2+ entry (SOCE) is a universal mechanism to increase intracellular Ca 2+ concentrations in non-excitable cells. It is initiated by the depletion of ER Ca 2+ stores, activation of stromal interaction molecule (STIM) 1 and gating of the Ca 2+ release activated Ca 2+ (CRAC) channel ORAI1 in the plasma membrane. We identified a minimal activation domain in the cytoplasmic region of STIM1 (CCb9) which activated Ca 2+ influx and CRAC currents ( I CRAC) in the absence of store depletion similar to but more potently than the entire C terminus of STIM1. A STIM1 fragment (CCb7) that is longer by 31 amino acids than CCb9 at its C terminal end showed reduced ability to constitutively activate I CRAC consistent with our observation that CCb9 but not CCb7 efficiently colocalized with and bound to ORAI1. Intracellular application of a 31 amino acid peptide contained in CCb7 but not CCb9 inhibited constitutive and store-dependent CRAC channel activation. In summary, these findings suggest that CCb9 represents a minimal ORAI1 activation domain within STIM1 that is masked by an adjacent 31 amino acid peptide preventing efficient CRAC channel activation in cells with replete Ca 2+ stores.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.05.020