OSCR

An axon-intrinsic loop restricts nerve regeneration through axonal protein synthesis.

Overview

Authors: Courtney N Buchanan1, Jinyoung Lee1, Samaneh Matoo1, Jordan A Headen1, Marie-Claire Honoree1, Molly Conway1, Lillian F Thompson2, Terika P Smith1, Ansley McKay1, Cailyn Tosadori1, Irene Dalla Costa1, Moira Lopez De Leon1, Elizabeth Thames1, Nora Perrone-Bizzozero3, Ashley L Kalinski1,4,5, Kristy Welshhans1,4,5, Lauren S Vaughn1,4, Jeffery L Twiss1,4,5
ORCID iDs: Courtney N Buchanan, Jinyoung Lee, Jordan A Headen, Molly Conway, Lillian F Thompson, Terika P Smith, Ansley McKay, Irene Dalla Costa, Elizabeth Thames, Nora Perrone-Bizzozero, Ashley L Kalinski, Kristy Welshhans, Lauren S Vaughn, Jeffery L Twiss
  1. Department of Biological Sciences, University of South Carolina; Columbia, SC 29204 USA
  2. Department of Chemistry & Biochemistry, University of Virginia; Charlottesville, VA 22904 USA
  3. Department of Neurosciences, University of New Mexico; Albuquerque, NM 87131 USA
  4. SmartState Center for Childhood Neurotherapeutics; University of South Carolina, Columbia, SC 29204 USA
  5. Carolina Autism and Neurodevelopment Center, University of South Carolina; Columbia, SC 29204 USA
Institutions: University of South Carolina (United States); University of Virginia (United States); University of New Mexico (United States)
Journal: Science advances, volume 12, issue 35, article eaed0049
Dates: received 10 October 2025; accepted 16 July 2026; published online 26 August 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1126/sciadv.aed0049 · PMID 42647628 · PMCID PMC13510589 · OpenAlex W4415675826
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.10.28.685020
Status: data only
Categories: cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, fMRI & imaging
MeSH: Axons*, Nerve Regeneration*, Protein Biosynthesis*, Animals, Axotomy, Calcium, Growth Cones, Pancreatitis-Associated Proteins, RNA, Messenger, RNA-Binding Proteins, Sciatic Nerve (* major topic)
Topic: Nerve injury and regeneration (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institutes of Health (R01-NS125146, R01-NS069833, R01-NS117821); NINDS NIH HHS (R01 NS125146, R01 NS117821); Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (N/A)
Citations: not cited yet (Europe PMC); 52 references in the paper

Abstract

Injured axons synthesize the RNA Binding Protein KHSRP that promotes mRNA decay and slows nerve regeneration. Axotomy-induced increase in axoplasmic Ca2+ activates axonal Khsrp translation, and while axonal Ca2+ returns to pre-injury levels within 16 hours post-axotomy, axonal KHSRP remains elevated. Alternating translation of Reg3a and Khsrp sustains KHSRP levels in regenerating axons. Axonal Reg3a mRNA and protein increase proximal to the injury site days after sciatic nerve crush. REG3A stimulates ER Ca2+ release in axons to activate PERK, increase eIF2α phosphorylation, and increase Khsrp translation. Axoplasmic Ca2+ slowly oscillates in growth cones of cultured neurons and Reg3a depletion attenuates growth cone Ca2+ oscillations, decreases KHSRP synthesis and reduces axonal retractive events in cultured neurons, and accelerates peripheral nerve regeneration in vivo. Thus, REG3A regulation of axonal KHSRP synthesis provides a signaling loop that decelerates axon growth through localized mRNA translation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data, code, and materials availability

Data included and and R code used here are publicly available on Zenodo online database (https://doi.org/10.5281/zenodo.21310717). cDNA contructs can be provided by L.S.V. and J.L.T. pending scientific review and a completed materials transfer agreement through the University of South Carolina.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 18 authors, 11 MeSH terms, 3 funders, 51 references.

Cite

This paper

Buchanan, C. N., Lee, J., Matoo, S., Headen, J. A., Honoree, M.-C., Conway, M., Thompson, L. F., Smith, T. P., McKay, A., Tosadori, C., Dalla Costa, I., Lopez De Leon, M., Thames, E., Perrone-Bizzozero, N., Kalinski, A. L., Welshhans, K., Vaughn, L. S., & Twiss, J. L. (2026). An axon-intrinsic loop restricts nerve regeneration through axonal protein synthesis. Science advances, 12(35), eaed0049. https://doi.org/10.1126/sciadv.aed0049

BibTeX

@article{buchanan2026axon,
author = {Buchanan, Courtney N and Lee, Jinyoung and Matoo, Samaneh and Headen, Jordan A and Honoree, Marie-Claire and Conway, Molly and Thompson, Lillian F and Smith, Terika P and McKay, Ansley and Tosadori, Cailyn and Dalla Costa, Irene and Lopez De Leon, Moira and Thames, Elizabeth and Perrone-Bizzozero, Nora and Kalinski, Ashley L and Welshhans, Kristy and Vaughn, Lauren S and Twiss, Jeffery L},
title = {{An axon-intrinsic loop restricts nerve regeneration through axonal protein synthesis}},
journal = {Science advances},
year = {2026},
month = aug,
volume = {12},
number = {35},
pages = {eaed0049},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aed0049},
url = {https://doi.org/10.1126/sciadv.aed0049},
pmid = {42647628},
pmcid = {PMC13510589}
}

RIS

TY - JOUR
AU - Buchanan, Courtney N
AU - Lee, Jinyoung
AU - Matoo, Samaneh
AU - Headen, Jordan A
AU - Honoree, Marie-Claire
AU - Conway, Molly
AU - Thompson, Lillian F
AU - Smith, Terika P
AU - McKay, Ansley
AU - Tosadori, Cailyn
AU - Dalla Costa, Irene
AU - Lopez De Leon, Moira
AU - Thames, Elizabeth
AU - Perrone-Bizzozero, Nora
AU - Kalinski, Ashley L
AU - Welshhans, Kristy
AU - Vaughn, Lauren S
AU - Twiss, Jeffery L
TI - An axon-intrinsic loop restricts nerve regeneration through axonal protein synthesis
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/08/26
VL - 12
IS - 35
SP - eaed0049
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aed0049
UR - https://doi.org/10.1126/sciadv.aed0049
LA - en
ER -

CSL-JSON

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