BioProject

STIM proteins play crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca2+ sensors. More...

STIM proteins play crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca2+ sensors. In neurons STIM2 was shown to have distinct functions from STIM1. However, its role in the brain activity and behavior was not fully elucidated. The aim of this work was to analyze the behavior of zebrafish (Danio rerio) lacking stim2a. We generated stim2a knockout zebrafish line using CRISPR/Cas9 system. The mutant animals had no morphological abnormalities and were fertile. RNA sequencing revealed altered gene expression of transcription factors such as egr4, fosab, fos1l, and npas4, as well as of several members of the calcium toolkit (CaTK) such as slc25a25b, anxa3a, grinab, hp, and hpca. Neuronal Ca2+ activity was measured in vivo in neurons expressing GCaMP5G sensor. Optic tectum neurons in stim2a-/- fish had more frequent Ca2+ signal oscillations as compared to neurons of wild type (WT) fish. We detected an increased activity during visual motor response (VMR) test, increased thigmotaxis in open field test, and disrupted phototaxis in dark/light preference in stim2a-/- mutants comparing to the WT. Both groups of animals reacted to glutamate and the GABA-ergic receptor antagonist pentylenetetrazol with an increase of activity during VMR but without major differences between them. The behavioral tests showed that the mobility of stim2a-/- fish was increased suggesting that they are hyperactive in comparison to WT fish. Altogether, our results suggest that hyperactive-like phenotype of stim2a-/- mutant is caused by dysregulation of Ca2+ homeostasis and signaling. Less...