STIM1 Ca2+ Sensor Control of L-type Ca2+-Channel-Dependent Dendritic Spine Structural Plasticity and Nuclear Signaling

• Published in: Cell reports (Cambridge) Vol. 19; no. 2; pp. 321 - 334
• Main Authors: Dittmer, Philip J., Wild, Angela R., Dell’Acqua, Mark L., Sather, William A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 11.04.2017; Elsevier
• Subjects: cytoplasmic Ca2; dendritic spine; endoplasmic reticulum; glutamate; L-type Ca2+ channel; N-methyl-D-aspartate receptor; nuclear factor of activated T cells; stromal interaction molecule 1; structural plasticity; voltage-gated Ca2+ channel; structural plasticity; nuclear factor of activated T cells; cytoplasmic Ca2; N-methyl-D-aspartate receptor; dendritic spine; voltage-gated Ca2+ channel; stromal interaction molecule 1; L-type Ca2+ channel; endoplasmic reticulum; glutamate
• DOI: 10.1016/j.celrep.2017.03.056
• ISSN: 2211-1247

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. [Display omitted] •NMDA receptor activation of L-type Ca2+ channels triggers Ca2+ release from ER•ER Ca2+ depletion activates STIM1, which feeds back onto L channels to inhibit them•Activated STIM1 promotes L-channel-dependent growth in dendritic spine ER content•Activated STIM1 attenuates L-channel-dependent nuclear translocation of NFAT Dittmer et al. show that postsynaptic activation of voltage-gated L-type Ca2+ channels triggers Ca2+ release from stores, activating feedback inhibition of L channels by the STIM1 Ca2+ sensor. Activated STIM1 also promotes L-channel-dependent growth in ER content of dendritic spines and attenuates nuclear translocation of the NFAT transcription factor.