title: STIM1 Ca2+Sensor Control of L-type Ca2+-Channel-Dependent Dendritic Spine Structural Plasticity and Nuclear Signaling.
abstract: Potentiation of synaptic strength relies on postsynaptic Ca2+signals, modification of dendritic spine structure, and changes in gene expression. One Ca2+signaling pathway supporting these processes routes through L-type Ca2+channels (LTCC), whose activity is subject to tuning by multiple mechanisms. Here, we show in hippocampal neurons that LTCC inhibition by the endoplasmic reticulum (ER) Ca2+sensor, stromal interaction molecule 1 (STIM1), is engaged by the neurotransmitter glutamate, resulting in regulation of spine ER structure and nuclear signaling by the NFATc3 transcription factor. In this mechanism, depolarization by glutamate activates LTCC Ca2+influx, releases Ca2+from the ER, and consequently drives STIM1 aggregation and an inhibitory interaction with LTCCs that increases spine ER content but decreases NFATc3 nuclear translocation. These findings of negative feedback control of LTCC signaling by STIM1 reveal interplay between Ca2+influx and release from stores that controls both postsynaptic structural plasticity and downstream nuclear signaling.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19(th) Avenue, Aurora, CO 80045, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Dittmer
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19(th) Avenue, Aurora, CO 80045, USA.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Wild
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19(th) Avenue, Aurora, CO 80045, USA. Electronic address: mark.dellacqua@ucdenver.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dell'Acqua
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19(th) Avenue, Aurora, CO 80045, USA. Electronic address: william.sather@ucdenver.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Sather
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics*; D020013:Calcium Signaling / Q000235:genetics*; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D050778:NFATC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D061251:Primary Cell Culture; D066329:Protein Aggregates / Q000235:genetics; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D000071737:Stromal Interaction Molecule 1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020746:Calcium Channels, L-Type; D050778:NFATC Transcription Factors; D066329:Protein Aggregates; D016194:Receptors, N-Methyl-D-Aspartate; D000071737:Stromal Interaction Molecule 1; C445503:transcription factor NF-AT c3; D018698:Glutamic Acid
keywords: L-type Ca(2+) channel; N-methyl-D-aspartate receptor; cytoplasmic Ca(2+); dendritic spine; endoplasmic reticulum; glutamate; nuclear factor of activated T cells; stromal interaction molecule 1; structural plasticity; voltage-gated Ca(2+) channel