Calcium Sensors STIM1 and STIM2 Regulate Different Calcium Functions in Cultured Hippocampal Neurons.

Liliya Kushnireva,Menahem Segal,Eduard Korkotian

doi:10.3389/fnsyn.2020.573714

Abstract

There are growing indications for the involvement of calcium stores in the plastic properties of neurons and particularly in dendritic spines of central neurons. The store-operated calcium entry (SOCE) channels are assumed to be activated by the calcium sensor stromal interaction molecule (STIM)which leads to activation of its associated Orai channel. There are two STIM species, and the differential role of the two in SOCE is not entirely clear. In the present study, we were able to distinguish between transfected STIM1, which is more mobile primarily in young neurons, and STIM2 which is less mobile and more prominent in older neurons in culture. STIM1 mobility is associated with spontaneous calcium sparks, local transient rise in cytosolic [Ca2+]i, and in the formation and elongation of dendritic filopodia/spines. In contrast, STIM2 is associated with older neurons, where it is mobile and moves into dendritic spines primarily when cytosolic [Ca2+]i levels are reduced, apparently to activate resident Orai channels. These results highlight a role for STIM1 in the regulation of [Ca2+]i fluctuations associated with the formation of dendritic spines or filopodia in the developing neuron, whereas STIM2 is associated with the maintenance of calcium entry into stores in the adult neuron.

Highlights

Calcium stores assume a critical role in the handling of cytosolic calcium concentration ([Ca2+]i) in neurons and non-neuronal cells alike (Verkhratsky, 2005; Zalk et al, 2007)
Since others and we have identified both STIM1 and STIM2 in hippocampal neurons, we explored the possibility that they are located at different neuronal compartments or possibly that they are expressed at different developmental ages and geared for different functions
There was a striking age-dependent difference in presence of STIM1&2 in dendritic protrusions, such that STIM1 was more prevalent in the 10 days in vitro cells (10 DIV), compared to STIM2 (Figure 2), and the other way around for the 20 DIV neurons

Summary

INTRODUCTION

Calcium stores assume a critical role in the handling of cytosolic calcium concentration ([Ca2+]i) in neurons and non-neuronal cells alike (Verkhratsky, 2005; Zalk et al, 2007). STIMs Regulate Different Calcium Functions tissue (Skibinska-Kijek et al, 2009; Segal and Korkotian, 2016), and STIM1/Orai can be converted from a dispersed to a punctate form upon depletion of calcium stores with thapsigargin (Klejman et al, 2009). They are important in the regulation of growth cone motility (Mitchell et al, 2012), in the regulation of voltage-gated calcium channels (Park et al, 2010), and in detrimental effects of chronic epilepsy (Steinbeck et al, 2011) and oxidative stress (Henke et al, 2013). STIM2, on the other hand, is active in the more mature neurons, where it is mobilized in response to a reduction of ambient [Ca2+]i and moves into dendritic spines

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT