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

Publication date: 11 April 2017
Source:Cell Reports, Volume 19, Issue 2
Author(s): Philip J. Dittmer, Angela R. Wild, Mark L. Dell'Acqua, William A. Sather
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.

Graphical abstract

Teaser

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.


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