Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons

Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

microRNA-2184 orchestrates Mauthner-cell axon regeneration in zebrafish via syt3 modulation

MicroRNAs(miRNAs)play a significant role in axon regeneration following spinal cord injury.However,the functions of numerous miRNAs in axon regeneration within the central nervous system(CNS)remain largely unexplored.Here,we elucidate the positive role of microRNA-2184(miR-2184)in axon regeneration within zebrafish Mauthner cells(M-cells).The upregulation of miR-2184 in a single M-cell can facilitate axon regeneration,while the specific sponge-induced silencing of miR-2184 leads to impeded regeneration.We show that syt3,a downstream target of miR-2184,negatively regulates axon regeneration,and the regeneration suppression modulated by syt3 depends on its binding to Ca2+.Furthermore,pharmacological stimulation of the cAMP/PKA pathway suggests that changes in the readily releasable pool may affect axon regeneration.Our data indicate that miR-2184 promotes axon regeneration of M-cells within the CNS by modulating the downstream target syt3,providing valuable insights into potential therapeutic strategies.