Store-operated cyclic AMP signalling mediated by STIM1

Lefkimmiatis, Konstantinos; Srikanthan, Meera; Maiellaro, Isabella; Moyer, Mary Pat; Curci, Silvana; Hofer, Aldebaran M.

Abstract

Depletion of Ca2+ from the endoplasmic reticulum (ER) results in activation of plasma membrane Ca2+ entry channels. This 'store-operated' process requires translocation of a transmembrane ER Ca2+ sensor protein, stromal interaction molecule 1 (STIM1), to sites closely apposed to Ca2+ channels at the cell surface. However, it is not known whether a reduction in Ca2+ stores is coupled to other signalling pathways by this mechanism. We found that lowering the concentration of free Ca2+ in the ER, independently of the cytosolic Ca2+ concentration, also led to recruitment of adenylyl cyclases. This resulted in enhanced cAMP accumulation and PKA activation, measured using FRET-based cAMP indicators. Translocation of STIM1 was required for efficient coupling of ER Ca2+ depletion to adenylyl cyclase activity. We propose the existence of a pathway (store-operated cAMP signalling or SOcAMPS) in which the content of internal Ca2+ stores is directly connected to cAMP signalling through a process that involves STIM1.

Citation

Lefkimmiatis, K., Srikanthan, M., Maiellaro, I., Moyer, M. P., Curci, S., & Hofer, A. M. (2009). Store-operated cyclic AMP signalling mediated by STIM1. Nature Cell Biology, 11(4), 433-442. https://doi.org/10.1038/ncb1850

• Journal Article Type: Article
• Acceptance Date: Dec 5, 2008
• Online Publication Date: Mar 15, 2009
• Publication Date: 2009-04
• Deposit Date: Apr 8, 2020
• Journal: Nature Cell Biology
• Print ISSN: 1465-7392
• Electronic ISSN: 1476-4679
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 4
• Pages: 433-442
• DOI: https://doi.org/10.1038/ncb1850
• Public URL: https://nottingham-repository.worktribe.com/output/4237837
• Publisher URL: https://www.nature.com/articles/ncb1850