HMW-3R-tau Promotes Axon Growth and Regeneration in Peripheral Neurons

Tau, a microtubule-associated protein abundant in neurons, is crucial for maintaining the structure and function of axons. Although tau alternative splicing in the central nervous system has been extensively studied, its implications in the peripheral nervous system (PNS) remain underexplored. In this study, rat dorsal root ganglion (DRG) were isolated and PCR cloning and DNA sequencing was employed to reveal the expression of 12 tau isoforms, attributed to the alternative splicing of exons 2, 3, 4A, and 10. The study further explored the differential expression of tau isoforms in PNS sensory and motor neurons across developmental stages and following injury. In vitro assays revealed a significant promotion of axonal growth by all tau isoforms, with HMW-3R-tau exhibiting the most pronounced effect. The axonal localization of HMW-3R-tau was found to positively correlate with axon length. Additionally, in vivo experiments utilizing MAPT knockout mice underscored the essential role of HMW-3R-tau in enhancing axonal regeneration post-sciatic nerve injury. These findings highlight the nuanced regulation of tau alternative splicing in the PNS and delineate the critical contribution of specific tau isoforms, particularly HMW-3R-tau, in fostering axonal growth and regeneration in the PNS.