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14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention.
Liu, Qiuling; Yang, Hua; Luo, Jianxian; Peng, Cheng; Wang, Ke; Zhang, Guowei; Lin, Hongsheng; Ji, Zhisheng.
Afiliación
  • Liu Q; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Yang H; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Luo J; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Peng C; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Wang K; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Zhang G; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Lin H; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Ji Z; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Elife ; 122024 Jan 17.
Article en En | MEDLINE | ID: mdl-38231910
ABSTRACT
Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The microtubule severing enzyme spastin is essential for axonal development and regeneration through remodeling of microtubule arrangement. To date, however, little is known regarding the mechanisms underlying spastin action in neural regeneration after spinal cord injury. Here, we use glutathione transferase pulldown and immunoprecipitation assays to demonstrate that 14-3-3 interacts with spastin, both in vivo and in vitro, via spastin Ser233 phosphorylation. Moreover, we show that 14-3-3 protects spastin from degradation by inhibiting the ubiquitination pathway and upregulates the spastin-dependent severing ability. Furthermore, the 14-3-3 agonist Fusicoccin (FC-A) promotes neurite outgrowth and regeneration in vitro which needs spastin activation. Western blot and immunofluorescence results revealed that 14-3-3 protein is upregulated in the neuronal compartment after spinal cord injury in vivo. In addition, administration of FC-A not only promotes locomotor recovery, but also nerve regeneration following spinal cord injury in both contusion and lateral hemisection models; however, the application of spastin inhibitor spastazoline successfully reverses these phenomena. Taken together, these results indicate that 14-3-3 is a molecular switch that regulates spastin protein levels, and the small molecule 14-3-3 agonist FC-A effectively mediates the recovery of spinal cord injury in mice which requires spastin participation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Axones Límite: Animals Idioma: En Revista: Elife Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Axones Límite: Animals Idioma: En Revista: Elife Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido