Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons
The regenerative potential of developing cortical axons depends on intrinsic mechanisms, such as axon-autonomous protein synthesis, that are still not fully understood. An emerging factor in this regenerative response is the bidirectional interplay between microtubule dynamics and the axonal ER. We hypothesize that locally synthesized ER proteins regulate microtubule dynamics and the regeneration of cortical axons. RNA data mining identified the ER-shaping protein Reticulon-1 as a relevant candidate across eight axonal transcriptomes. Using microfluidics, we show that axonal treatment with a small RNA against Reticulon-1 mRNA (Reticulon-1 knockdown) increases outgrowth of injured cortical axons while reducing their tubulin levels. We show by live-cell imaging that axonal Reticulon-1 knockdown increases microtubule growth rate in noninjured axons and restores this parameter after injury. Axonal inhibition of the microtubule-severing protein Spastin prevents the effects of Reticulon-1 knockdown over tubulin levels and outgrowth. We provide evidence that the Reticulon-1C isoform is synthesized within axons and attenuates Spastin-mediated microtubule severing. These findings support a model in which axonal protein synthesis regulates microtubule dynamics and axon outgrowth after injury.
Authors
- Alejandro Luarte (ORCID: https://orcid.org/0000-0001-9138-1854)
- Rodrigo Herrera‐Molina (ORCID: https://orcid.org/0000-0001-9597-5131)
- Daniela Corvalán
- Francisca Bertin (ORCID: https://orcid.org/0000-0001-9634-1931)
- Ulrich Hengst (ORCID: https://orcid.org/0000-0002-8061-2861)
- Ankush Chakraborty (ORCID: https://orcid.org/0000-0003-4525-5667)
- Javiera Andrea Ojeda Gallardo
- Waldo Acevedo (ORCID: https://orcid.org/0000-0002-1182-0253)
- André Alberto Weber (ORCID: https://orcid.org/0000-0003-1999-0780)
- Cláudio Gouveia Roque (ORCID: https://orcid.org/0000-0003-3768-9633)
- Úrsula Wyneken (ORCID: https://orcid.org/0000-0001-8913-4475)
- Andrés Couve
- C. Contreras
- Christian Enrique González-Billault
- Jorge Toledo (ORCID: https://orcid.org/0000-0001-8678-558X)
- Tatiana Adasme-Rocha (ORCID: https://orcid.org/0000-0002-0840-1912)
- Juan Pablo Ramírez
- Antonia Figueroa
- Werner Zuschratter
- Andrea Paula-Lima
Institutions
- Pontificia Universidad Católica de Valparaíso (CL)
- Universidad del Desarrollo (CL)
- Buck Institute for Research on Aging (US)
- Neurosciences Institute (US)
- George Washington University (US)
- Adolfo Ibáñez University (CL)
- Clínica Alemana (CL)
- Metropolitan University of Educational Sciences (CL)
- Universidad Bernardo O'Higgins (CL)
- University of the Americas (CL)
- Hospital Clínico de la Universidad de Chile (CL)
- Instituto de Neurociencia Biomédica (CL)
- Universidad de Los Andes (BO)
- Photonamic (Germany) (DE)
- Universidad de Aysén (CL)
- University of Chile (CL)
- Columbia University (US)
- Leibniz Institute for Neurobiology (DE)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2026-01-06
- DOI
- https://doi.org/10.26508/lsa.202503571
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00