Proteolytic cleavage of G3BP1 by calpain 1 couples NMDAR activation to mTOR-dependent local translation.
Overview
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
- Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul, South Korea
- Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul, South Korea
Abstract
Ribonucleoprotein (RNP) granules are dynamic, membraneless organelles that sequester translationally repressed mRNAs and RNA-binding proteins, playing a pivotal role in the regulation of localized protein synthesis. While disassembly of RNP granules is essential for reactivating translation, the mechanisms by which neuronal activity regulates this process remain poorly understood. In this study, we show that stimulation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) triggers calcium influx, leading to activation of calpain 1 and subsequent proteolytic cleavage of Ras-GTPase-activating protein binding protein 1 (G3BP1), a core component of stress granules. This cleavage results in the disassembly of G3BP1 granules in the neurites and promotes mTOR-dependent local translation, thereby linking synaptic activity to spatially restricted protein synthesis. Finally, we demonstrate that the NMDAR–calpain 1–G3BP1–mTOR signaling axis contributes to axonal regeneration, establishing proteolytic remodeling of RNP granules as a key mechanism of activity-dependent neural repair.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Data links
- ebi.ac.uk/
biostudies/ , EMBL-EBI; found in the text, “Author contributions”sourcedata
Data availability
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The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_103
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 2 keywords, 17 MeSH terms, 3 funders, 59 references, 4 RRIDs.
Cite
This paper
Park, D.-h., Ahn, S.-Y., Kim, J., Choi, J., Lee, S., Kang, M., Song, J.-m., & Suh, Y. H. (2026). Proteolytic cleavage of G3BP1 by calpain 1 couples NMDAR activation to mTOR-dependent local translation. EMBO reports, 27(10), 2749-2771. https://
BibTeX
@article{park2026proteol
author = {Park, Da-ha and Ahn, So-Young and Kim, Jungho and Choi, Jiwoo and Lee, Seungha and Kang, Minji and Song, Jae-man and Suh, Young Ho},
title = {{Proteolytic cleavage of G3BP1 by calpain 1 couples NMDAR activation to mTOR-dependent local translation}},
journal = {EMBO reports},
year = {2026},
month = apr,
volume = {27},
number = {10},
pages = {2749--2771},
publisher = {Nature Publishing Group},
issn = {1469-221X},
doi = {10.1038/
url = {https://
pmid = {41935238},
pmcid = {PMC13219515}
}
RIS
TY - JOUR
AU - Park, Da-ha
AU - Ahn, So-Young
AU - Kim, Jungho
AU - Choi, Jiwoo
AU - Lee, Seungha
AU - Kang, Minji
AU - Song, Jae-man
AU - Suh, Young Ho
TI - Proteolytic cleavage of G3BP1 by calpain 1 couples NMDAR activation to mTOR-dependent local translation
T2 - EMBO reports
J2 - EMBO Rep
PY - 2026
DA - 2026/
VL - 27
IS - 10
SP - 2749
EP - 2771
SN - 1469-221X
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
{
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"container-title": "EMBO reports",
"author": [
{
"family": "Park",
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"given": "Young Ho"
}
],
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"PMCID": "PMC13219515",
"ISSN": "1469-221X",
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"URL": "https://
"language": "en",
"issued": {
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