Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons
Alejandro Luarte, Javiera Gallardo, 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
TL;DR
This study shows that Reticulon-1, a protein in axons, controls microtubule dynamics and axon regrowth after injury.
Contribution
The study reveals that axonal Reticulon-1 synthesis regulates microtubule severing and axon outgrowth after injury.
Findings
Reticulon-1 knockdown increases injured cortical axon outgrowth and microtubule growth rate.
Reticulon-1C isoform attenuates Spastin-mediated microtubule severing in axons.
Axonal Reticulon-1 synthesis influences tubulin levels and regeneration after injury.
Abstract
This study provides evidence that synthesis of Reticulon-1 restrains Spastin-mediated microtubule severing with implications for cortical axon outgrowth after injury. 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…
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Taxonomy
TopicsNerve injury and regeneration · Neurogenesis and neuroplasticity mechanisms · Axon Guidance and Neuronal Signaling