Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons

Alejandro Luarte; GALLARDO ROJAS, JAVIERA CAROLINA; Daniela Corvalán; Ankush Chakraborty; Cláudio Gouveia Roque; Francisca Bertin; Carlos Contreras; Juan Pablo Ramírez; André Weber; Waldo Acevedo; Werner Zuschratter; Rodrigo Herrera-Molina; Úrsula Wyneken; Andrea Paula-Lima; Tatiana Adasme-Rocha; Jorge Toledo; Rodrigo Vergara; Antonia Figueroa; Carolina González; Christian González-Billault

doi:10.26508/lsa.202503571

Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons

Journal

Life Science Alliance

ISSN

2575-1077

Date Issued

2026-01-16

Author(s)

Alejandro Luarte

GALLARDO ROJAS, JAVIERA CAROLINA

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Daniela Corvalán

Ankush Chakraborty

Cláudio Gouveia Roque

Francisca Bertin

Carlos Contreras

Juan Pablo Ramírez

André Weber

Waldo Acevedo

Werner Zuschratter

Rodrigo Herrera-Molina

Úrsula Wyneken

Andrea Paula-Lima

Tatiana Adasme-Rocha

Jorge Toledo

Rodrigo Vergara

Antonia Figueroa

Carolina González

Christian González-Billault

Ulrich Hengst

Andrés Couve

Type

journal-article

DOI

10.26508/lsa.202503571

URL

https://hdl.handle.net/123456789/12101

Abstract

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.