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Oligomerization and Ca2+/calmodulin control binding of the ER Ca2+-sensors STIM1 and STIM2 to plasma membrane lipids
- Source :
- Bioscience Reports, Vol 33, Iss 5, p e00077 (2013), Bioscience Reports
- Publication Year :
- 2013
- Publisher :
- Portland Press Ltd., 2013.
-
Abstract
- Ca2+ (calcium) homoeostasis and signalling rely on physical contacts between Ca2+ sensors in the ER (endoplasmic reticulum) and Ca2+ channels in the PM (plasma membrane). STIM1 (stromal interaction molecule 1) and STIM2 Ca2+ sensors oligomerize upon Ca2+ depletion in the ER lumen, contact phosphoinositides at the PM via their cytosolic lysine (K)-rich domains, and activate Ca2+ channels. Differential sensitivities of STIM1 and STIM2 towards ER luminal Ca2+ have been studied but responses towards elevated cytosolic Ca2+ concentration and the mechanism of lipid binding remain unclear. We found that tetramerization of the STIM1 K-rich domain is necessary for efficient binding to PI(4,5)P2-containing PM-like liposomes consistent with an oligomerization-driven STIM1 activation. In contrast, dimerization of STIM2 K-rich domain was sufficient for lipid binding. Furthermore, the K-rich domain of STIM2, but not of STIM1, forms an amphipathic α-helix. These distinct features of the STIM2 K-rich domain cause an increased affinity for PI(4,5)P2, consistent with the lower activation threshold of STIM2 and a function as regulator of basal Ca2+ levels. Concomitant with higher affinity for PM lipids, binding of CaM (calmodulin) inhibited the interaction of the STIM2 K-rich domain with liposomes in a Ca2+ and PI(4,5)P2 concentration-dependent manner. Therefore we suggest that elevated cytosolic Ca2+ concentration down-regulates STIM2-mediated ER–PM contacts via CaM binding.
- Subjects :
- Phosphatidylinositol 4,5-Diphosphate
NCBI, National Center for Biotechnology Information
lcsh:Life
lcsh:QR1-502
Biochemistry
Protein Structure, Secondary
lcsh:Microbiology
PC, phosphatidylcholine
ER–PM contact site
GFP, green fluorescent protein
CaM, calmodulin
store-operated calcium entry (SOCE)
K-rich domain
biology
Chemistry
Ca2+, calcium
STIM1
phosphoinositides
STIM2
CTD, C-terminal domain
Neoplasm Proteins
Cell biology
PM, plasma membrane
Protein Binding
Binding domain
Calmodulin
Membrane lipids
Biophysics
SDM, site-directed mutagenesis
SOCE, store-operated calcium entry
Binding, Competitive
S5
CC, coiled-coil
n.s., not significant
ER, endoplasmic reticulum
Membrane Lipids
Humans
Protein Interaction Domains and Motifs
Stromal Interaction Molecule 1
Stromal Interaction Molecule 2
Binding site
Molecular Biology
CAD, channel-activation domain
SAM, sterile alpha motif
Original Paper
KPi, potassium phosphate
Binding Sites
Endoplasmic reticulum
Membrane Proteins
Cell Biology
lcsh:QH501-531
DTT, dithiothreitol
Liposomes
biology.protein
STIM, stromal interaction molecule
Calcium
Protein Multimerization
calmodulin (CaM)
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 15734935 and 01448463
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Bioscience Reports
- Accession number :
- edsair.doi.dedup.....a0e2bf3957fd12a14201e577aac8f413
- Full Text :
- https://doi.org/10.1042/bsr20130089