Presynaptic store-operated Ca²⁺ entry drives excitatory spontaneous neurotransmission and augments endoplasmic reticulum stress.

ABSTRACT: Store-operated calcium entry (SOCE) is activated by depletion of Ca²⁺ from the endoplasmic reticulum (ER) and mediated by stromal interaction molecule (STIM) proteins. Here, we show that in rat and mouse hippocampal neurons, acute ER Ca²⁺ depletion increases presynaptic Ca²⁺ levels and glutamate release through a pathway dependent on STIM2 and the synaptic Ca²⁺ sensor synaptotagmin-7 (syt7). In contrast, synaptotagmin-1 (syt1) can suppress SOCE-mediated spontaneous release, and STIM2 is required for the increase in spontaneous release seen during syt1 loss of function. We also demonstrate that chronic ER stress activates the same pathway leading to syt7-dependent potentiation of spontaneous glutamate release. During ER stress, inhibition of SOCE

SUBMITTER: Chanaday NL 

PROVIDER: S-EPMC8068669 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature