Divergent interplay between STIM1 and STIM2 sets the efficacy of central synapses.

Authors

Jiangnan Xiao, Jahleel D Torres-Pérez, Eve Gautreaux, A Alejandro Vilcaes, Natali L Chanaday

Published in

Cell reports. Volume 45. Issue 10. Pages 118153. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Stromal interaction molecules (STIMs) are endoplasmic reticulum resident calcium (Ca²⁺ sensors that modulate Ca²⁺ homeostasis. Mammals express two isoforms, STIM1 and STIM2, but whether they serve redundant or distinct roles in neurotransmission remains poorly defined. Using Ca²⁺ imaging and electrophysiology in hippocampal neurons lacking STIM1, STIM2, or both, we examined presynaptic and postsynaptic functions of STIMs at excitatory and inhibitory synapses. Both isoforms redundantly activated store-operated Ca²⁺ entry and amplified presynaptic Ca²⁺ influx, sustaining neurotransmitter release by expanding the readily releasable pool of synaptic vesicles and accelerating vesicle replenishment. These presynaptic roles were synapse specific: STIM1 predominantly supported excitatory synapses, whereas STIM2 was critical for the inhibitory counterparts. Postsynaptically, STIM1 and STIM2 exerted opposing effects on glutamate and GABA receptor levels, such that simultaneous loss of both isoforms rescued postsynaptic function. Together, the findings show that STIM1 and STIM2 differentially tune synaptic efficacy according to synapse type and subcellular compartment.

PMID:
42886555
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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