NEUROD2 Regulates Stim1 Expression and Store-Operated Calcium Entry in Cortical Neurons

eNeuro. 2017 Mar 9;4(1):ENEURO.0255-16.2017. doi: 10.1523/ENEURO.0255-16.2017. eCollection 2017 Jan-Feb.


Calcium signaling controls many key processes in neurons, including gene expression, axon guidance, and synaptic plasticity. In contrast to calcium influx through voltage- or neurotransmitter-gated channels, regulatory pathways that control store-operated calcium entry (SOCE) in neurons are poorly understood. Here, we report a transcriptional control of Stim1 (stromal interaction molecule 1) gene, which is a major sensor of endoplasmic reticulum (ER) calcium levels and a regulator of SOCE. By using a genome-wide chromatin immunoprecipitation and sequencing approach in mice, we find that NEUROD2, a neurogenic transcription factor, binds to an intronic element within the Stim1 gene. We show that NEUROD2 limits Stim1 expression in cortical neurons and consequently fine-tunes the SOCE response upon depletion of ER calcium. Our findings reveal a novel mechanism that regulates neuronal calcium homeostasis during cortical development.

Keywords: Neurod2; calcium; genomics; store-operated calcium entry; transcription factor.

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Calcium / metabolism*
  • Cell Cycle Proteins
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism
  • Conserved Sequence
  • Endoplasmic Reticulum / metabolism*
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Introns
  • Mice, Inbred BALB C
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Nuclear Proteins
  • Protein Binding
  • Stromal Interaction Molecule 1 / metabolism*
  • Transcription Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • MCIDAS protein, human
  • Neurod2 protein, mouse
  • Neuropeptides
  • Nuclear Proteins
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • Transcription Factors
  • Calcium