Work

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

Year: 2026

Type: article

Abstract: Stromal interaction molecules (STIMs) are endoplasmic reticulum resident calcium (Ca 2+ sensors that modulate Ca 2+ homeostasis. Mammals express two isoforms, STIM1 and STIM2, but whether they serve redundant or distinct roles in neurotransmission remains poorly defined. Using Ca 2+ 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 Ca 2+ entry and amplified presynaptic Ca 2+ 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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118153

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

Institutions: University of Connecticut, University of Puerto Rico at Río Piedras, University of Puerto Rico System, University of Pennsylvania

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,620

Funders: Whitehall Foundation, University of Pennsylvania, Margaret Q. Landenberger Research Foundation