Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain.
Overview
- Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), Bld. 48, Saarland University, Campus Homburg, Homburg 66421, Germany
- Center for Bioinformatics, Saarland University, Campus Saarbruecken, Saarbrueken 66123, Germany
- Institute of Anatomy and Cell Biology, Saarland University, Campus Homburg, Homburg 66421, Germany
- Department of Theoretical Physics, Saarland University, Campus Saarbruecken, Saarbrueken 66123, Germany
- Center for Biophysics, Saarland University, Campus Saarbruecken, Saarbrueken 66123, Germany
Abstract
Ca2+ homeostasis is essential for cellular functions, with regulation by store-operated Ca2+ entry (SOCE) omnipresent. Due to a lower affinity for endoplasmic reticulum (ER)-luminal Ca2+, STIM2 regulates basal cytosolic Ca2+ but also increases interaction and activation of ORAI proteins at ER–plasma membrane junctions after stimulation, whereas STIM1 requires stronger store depletion. In brain, STIM2 is highly expressed in hippocampal neurons. Here, we describe a short STIM2 splice variant, STIM2.3 (also known as STIM2G), that is present only in Old World monkeys, apes and humans, with expression mostly in brain. In contrast to other variants and despite lack of the polybasic domain, expression of STIM2.3 increased SOCE. Structure–function analysis delineated the role of the C-terminal motifs of STIM2 for Ca2+ entry as well as for basal and induced activation of the NFAT transcription factor NFATc1. STIM2.3 displayed reduced interaction with AMPK and with activated AMPK. Neuronal expression of STIM2.3, in comparison to STIM2.2, increased the size of dendritic spine heads, suggesting a specific regulatory role in spine maintenance. Regulated splicing of STIM2.3 in brain might present a rapid mechanism to increase STIM2-mediated effects on gene expression, spine morphology or spontaneous excitability, potentially facilitating an evolutionarily recent expansion of brain complexity.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- arrayexpress:E-MTAB-4840
, at ArrayExpress; found in the text, “Bioinformatics” - uniprot.org/
uniprotkb/ , at UniProt; found in the text, “RESULTS”a0a8v8tmc8 - uniprot.org/
uniprotkb/ , at UniProt; found in the text, “RESULTS”h7c5a5 - uniprot.org/
uniprotkb/ , at UniProt; found in the text, “RESULTS”q9p246
Versions
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Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 6 keywords, 12 MeSH terms, 2 funders, 83 references.
Cite
This paper
Poth, V., Do, H. T. T., Jarzembowski, L., Laius, K.-L., Förderer, K., Tschernig, T., Robertson, H. B., Alansary, D., Shaebani, R., Helms, V., & Niemeyer, B. A. (2026). Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain. Journal of cell science, 139(8), jcs264353. https://
BibTeX
@article{poth2026alterna
author = {Poth, Vanessa and Do, Hoang Thu Trang and Jarzembowski, Lukas and Laius, Katrin-Lisa and Förderer, Kathrin and Tschernig, Thomas and Robertson, Hanah B. and Alansary, Dalia and Shaebani, Reza and Helms, Volkhard and Niemeyer, Barbara A.},
title = {{Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain}},
journal = {Journal of cell science},
year = {2026},
month = apr,
volume = {139},
number = {8},
pages = {jcs264353},
publisher = {The Company of Biologists},
issn = {0021-9533},
doi = {10.1242/
url = {https://
pmid = {41766388},
pmcid = {PMC13143212}
}
RIS
TY - JOUR
AU - Poth, Vanessa
AU - Do, Hoang Thu Trang
AU - Jarzembowski, Lukas
AU - Laius, Katrin-Lisa
AU - Förderer, Kathrin
AU - Tschernig, Thomas
AU - Robertson, Hanah B.
AU - Alansary, Dalia
AU - Shaebani, Reza
AU - Helms, Volkhard
AU - Niemeyer, Barbara A.
TI - Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain
T2 - Journal of cell science
J2 - J Cell Sci
PY - 2026
DA - 2026/
VL - 139
IS - 8
SP - jcs264353
SN - 0021-9533
PB - The Company of Biologists
DO - 10.1242/
UR - https://
LA - en
ER -
CSL-JSON
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