Abstract
STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca2+ sensors, coupling directly to activate plasma membrane Orai Ca2+ entry channels. Despite extensive sequence homology, the STIM proteins are functionally distinct. We reveal that the short variable N-terminal random coil sequences of STIM1 and STIM2 confer profoundly different activation properties. Using Orai1-expressing HEK293 cells, chimeric replacement of the 43-amino-acid STIM1 N terminus with that of STIM2 attenuates Orai1-mediated Ca2+ entry and drastically slows store-induced Orai1 channel activation. Conversely, the 55-amino-acid STIM2 terminus substituted within STIM1 strikingly enhances both Orai1-mediated Ca2+ entry and constitutive coupling to activate Orai1 channels. Hence, STIM N termini are powerful coupling modifiers, functioning in STIM2 to "brake" the otherwise constitutive activation of Orai1 channels afforded by its high sensitivity to luminal Ca2+.
Original language | English |
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Pages (from-to) | 19164-19168 |
Number of pages | 4 |
Journal | Journal of Biological Chemistry |
Volume | 284 |
Issue number | 29 |
DOIs | |
State | Published - Jul 17 2009 |
Keywords
- Blotting, Western
- Calcium Channels/genetics
- Calcium/metabolism
- Cell Adhesion Molecules/chemistry
- Cell Line
- Humans
- Kinetics
- Membrane Potentials
- Membrane Proteins/chemistry
- Neoplasm Proteins/chemistry
- ORAI1 Protein
- Patch-Clamp Techniques
- Recombinant Fusion Proteins/genetics
- Stromal Interaction Molecule 1
- Stromal Interaction Molecule 2
- Transfection