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Store-operated cyclic AMP signalling mediated by STIM1
Konstantinos Lefkimmiatis1, Meera Srikanthan, Isabella Maiellaro
1VA Boston Healthcare System and the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, West Roxbury, Massachusetts 02132, USA.
Nature Cell Biology
|March 17, 2009
Summary
Endoplasmic reticulum (ER) calcium depletion activates adenylyl cyclase and cAMP signaling. This store-operated cAMP signaling (SOcAMPS) pathway requires STIM1 translocation for coupling ER calcium levels to adenylyl cyclase activity.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Calcium Homeostasis
Background:
- Endoplasmic reticulum (ER) calcium (Ca2+) depletion activates plasma membrane Ca2+ entry channels via STIM1 translocation.
- The coupling of ER Ca2+ store reduction to other signaling pathways remains largely unexplored.
Purpose of the Study:
- To investigate whether ER Ca2+ depletion, independently of cytosolic Ca2+ levels, influences other signaling pathways.
- To elucidate the role of STIM1 in coupling ER Ca2+ levels to downstream signaling events.
Main Methods:
- Utilized FRET-based cAMP indicators to measure cAMP accumulation.
- Monitored adenylyl cyclase recruitment and PKA activation.
- Assessed the requirement of STIM1 translocation for signaling pathway coupling.
Main Results:
- ER Ca2+ depletion, independent of cytosolic Ca2+ concentration, induced adenylyl cyclase recruitment.
- This process led to enhanced cAMP accumulation and PKA activation.
- STIM1 translocation was essential for efficient coupling of ER Ca2+ depletion to adenylyl cyclase activity.
Conclusions:
- A novel pathway, termed store-operated cAMP signaling (SOcAMPS), connects internal Ca2+ store content to cAMP signaling.
- STIM1 acts as a crucial mediator in the SOcAMPS pathway, linking ER Ca2+ levels to adenylyl cyclase activity.
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