PUBLICATION

Thymosin β4 promotes zebrafish Mauthner axon regeneration by facilitating actin polymerization through binding to G-actin

Authors
Song, Z., Han, A., Hu, B.
ID
ZDB-PUB-241025-2
Date
2024
Source
BMC Biology   22: 244244 (Journal)
Registered Authors
Hu, Bing
Keywords
Axon regeneration, C-start, G-actin, Mauthner, Proportion of straight tails, Thymosin beta 4
MeSH Terms
  • Larva/metabolism
  • Larva/physiology
  • Axons*/metabolism
  • Axons*/physiology
  • Actins*/metabolism
  • Zebrafish*/physiology
  • Polymerization
  • Nerve Regeneration*/physiology
  • Thymosin*/genetics
  • Thymosin*/metabolism
  • Animals
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
39443925 Full text @ BMC Biol.
Abstract
Thymosin beta 4 (Tβ4) is a monomeric actin-binding protein that plays many roles in biological activities. However, some studies on the role of Tβ4 in central axon regeneration have yielded contradictory results. Previous research has focused primarily on cultured cells, leading to a deficiency in in vivo experimental evidence. Therefore, we used a single axon injury model of Mauthner cells in zebrafish larvae to investigate the role of Tβ4 in central axon regeneration in vivo.
Our results demonstrated that knockout of Tβ4 impaired axon regeneration, whereas overexpression of Tβ4 promoted axon regeneration. Moreover, this promotion is mediated through the interaction between Tβ4 and G-actin. Furthermore, our results suggest that the binding of Tβ4 to G-actin promotes actin polymerization rather than depolymerization. In the rapid escape behavior test, larvae with damaged axons presented impaired tail muscle control, resulting in a lack of normal tail bending, termed the straight tail phenomenon. The proportion of straight tails was significantly negatively correlated with axon regeneration length, suggesting that it is a new indicator for assessing rapid escape behavior recovery. Finally, the results showed that the overexpression of Tβ4 effectively restored the functionality of rapid escape behaviors mediated by Mauthner cells.
Our results provide evidence that Tβ4 promotes central axon regeneration in vivo through binding to G-actin and suggest that Tβ4 could serve as a potential polypeptide drug for clinical therapy.
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