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cAMP induces stromal interaction molecule 1 (STIM1) puncta but neither Orai1 protein clustering nor store-operated Ca2+ entry (SOCE) in islet cells.
J Biol Chem 2012; 287(13):9862-72JB

Abstract

The events leading to the activation of store-operated Ca(2+) entry (SOCE) involve Ca(2+) depletion of the endoplasmic reticulum (ER) resulting in translocation of the transmembrane Ca(2+) sensor protein, stromal interaction molecule 1 (STIM1), to the junctions between ER and the plasma membrane where it binds to the Ca(2+) channel protein Orai1 to activate Ca(2+) influx. Using confocal and total internal reflection fluorescence microscopy, we studied redistribution kinetics of fluorescence-tagged STIM1 and Orai1 as well as SOCE in insulin-releasing β-cells and glucagon-secreting α-cells within intact mouse and human pancreatic islets. ER Ca(2+) depletion triggered accumulation of STIM1 puncta in the subplasmalemmal ER where they co-clustered with Orai1 in the plasma membrane and activated SOCE. Glucose, which promotes Ca(2+) store filling and inhibits SOCE, stimulated retranslocation of STIM1 to the bulk ER. This effect was evident at much lower glucose concentrations in α- than in β-cells consistent with involvement of SOCE in the regulation of glucagon secretion. Epinephrine stimulated subplasmalemmal translocation of STIM1 in α-cells and retranslocation in β-cells involving raising and lowering of cAMP, respectively. The cAMP effect was mediated both by protein kinase A and exchange protein directly activated by cAMP. However, the cAMP-induced STIM1 puncta did not co-cluster with Orai1, and there was no activation of SOCE. STIM1 translocation can consequently occur independently of Orai1 clustering and SOCE.

Authors+Show Affiliations

Department of Medical Cell Biology, Uppsala University, BMC Box 571, SE-751 23 Uppsala, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22298778

Citation

Tian, Geng, et al. "CAMP Induces Stromal Interaction Molecule 1 (STIM1) Puncta but Neither Orai1 Protein Clustering nor Store-operated Ca2+ Entry (SOCE) in Islet Cells." The Journal of Biological Chemistry, vol. 287, no. 13, 2012, pp. 9862-72.
Tian G, Tepikin AV, Tengholm A, et al. CAMP induces stromal interaction molecule 1 (STIM1) puncta but neither Orai1 protein clustering nor store-operated Ca2+ entry (SOCE) in islet cells. J Biol Chem. 2012;287(13):9862-72.
Tian, G., Tepikin, A. V., Tengholm, A., & Gylfe, E. (2012). CAMP induces stromal interaction molecule 1 (STIM1) puncta but neither Orai1 protein clustering nor store-operated Ca2+ entry (SOCE) in islet cells. The Journal of Biological Chemistry, 287(13), pp. 9862-72. doi:10.1074/jbc.M111.292854.
Tian G, et al. CAMP Induces Stromal Interaction Molecule 1 (STIM1) Puncta but Neither Orai1 Protein Clustering nor Store-operated Ca2+ Entry (SOCE) in Islet Cells. J Biol Chem. 2012 Mar 23;287(13):9862-72. PubMed PMID: 22298778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - cAMP induces stromal interaction molecule 1 (STIM1) puncta but neither Orai1 protein clustering nor store-operated Ca2+ entry (SOCE) in islet cells. AU - Tian,Geng, AU - Tepikin,Alexei V, AU - Tengholm,Anders, AU - Gylfe,Erik, Y1 - 2012/02/01/ PY - 2012/2/3/entrez PY - 2012/2/3/pubmed PY - 2012/5/17/medline SP - 9862 EP - 72 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 287 IS - 13 N2 - The events leading to the activation of store-operated Ca(2+) entry (SOCE) involve Ca(2+) depletion of the endoplasmic reticulum (ER) resulting in translocation of the transmembrane Ca(2+) sensor protein, stromal interaction molecule 1 (STIM1), to the junctions between ER and the plasma membrane where it binds to the Ca(2+) channel protein Orai1 to activate Ca(2+) influx. Using confocal and total internal reflection fluorescence microscopy, we studied redistribution kinetics of fluorescence-tagged STIM1 and Orai1 as well as SOCE in insulin-releasing β-cells and glucagon-secreting α-cells within intact mouse and human pancreatic islets. ER Ca(2+) depletion triggered accumulation of STIM1 puncta in the subplasmalemmal ER where they co-clustered with Orai1 in the plasma membrane and activated SOCE. Glucose, which promotes Ca(2+) store filling and inhibits SOCE, stimulated retranslocation of STIM1 to the bulk ER. This effect was evident at much lower glucose concentrations in α- than in β-cells consistent with involvement of SOCE in the regulation of glucagon secretion. Epinephrine stimulated subplasmalemmal translocation of STIM1 in α-cells and retranslocation in β-cells involving raising and lowering of cAMP, respectively. The cAMP effect was mediated both by protein kinase A and exchange protein directly activated by cAMP. However, the cAMP-induced STIM1 puncta did not co-cluster with Orai1, and there was no activation of SOCE. STIM1 translocation can consequently occur independently of Orai1 clustering and SOCE. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/22298778/cAMP_induces_stromal_interaction_molecule_1__STIM1__puncta_but_neither_Orai1_protein_clustering_nor_store_operated_Ca2+_entry__SOCE__in_islet_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=22298778 DB - PRIME DP - Unbound Medicine ER -