Garcia-Alvarez, Gisela Lu, Bo Yap, Kenrick An Fu Wong, Loo Chin Thevathasan, Jervis Vermal Lim, Lynette Ji, Fang Tan, Kia Wee Mancuso, James J. Tang, Willcyn Poon, Shou Yu Augustine, George J. Fivaz, Marc 2024-01-20T07:32:32Z 2024-01-20T07:32:32Z 2022-01-25 2015-03 1059-1524 https://pubs.kist.re.kr/handle/201004/125678 STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER-plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites. English AMER SOC CELL BIOLOGY STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs Article 10.1091/mbc.E14-07-1222 1 MOLECULAR BIOLOGY OF THE CELL, v.26, no.6, pp.1141 - 1159 MOLECULAR BIOLOGY OF THE CELL 26 6 1141 1159 N scie scopus 000351945900011 2-s2.0-84924953196 Cell Biology Cell Biology Article INTERACTION MOLECULE-1 STIM1 OPERATED CA2+ ENTRY ENDOPLASMIC-RETICULUM SYNAPTIC PLASTICITY DENDRITIC SPINES PROTEIN-KINASE POSTSYNAPTIC DENSITIES STORE CALCIUM RECEPTORS