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Published on: October 30, 2018
HMW-3R-tau Promotes Axon Growth and Regeneration in Peripheral Neurons
Dandan Chu1, Fuchao Zhang2,3, Jing Zhang1
1Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, Jiangsu, China.
This study reveals that specific tau isoforms, particularly high molecular weight-3 repeat tau (HMW-3R-tau), significantly promote axonal growth and regeneration in the peripheral nervous system (PNS). These findings are crucial for understanding nerve repair mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Peripheral Nervous System Research
Background:
- Tau protein is vital for neuronal structure and axon function.
- Tau alternative splicing in the central nervous system is well-studied, but its role in the peripheral nervous system (PNS) is less understood.
Purpose of the Study:
- To investigate tau alternative splicing in the rat peripheral nervous system.
- To determine the effects of different tau isoforms on axonal growth and regeneration.
- To elucidate the role of specific tau isoforms in PNS development and injury response.
Main Methods:
- Isolation of rat dorsal root ganglion (DRG) neurons.
- PCR cloning and DNA sequencing to identify tau isoforms.
- In vitro assays for axonal growth promotion.
- In vivo studies using MAPT knockout mice after sciatic nerve injury.
Main Results:
- Identified 12 tau isoforms in rat DRG due to alternative splicing of exons 2, 3, 4A, and 10.
- All tau isoforms promoted axonal growth in vitro, with HMW-3R-tau showing the strongest effect.
- HMW-3R-tau axonal localization correlated positively with axon length.
- HMW-3R-tau was essential for axonal regeneration in vivo after sciatic nerve injury in MAPT knockout mice.
Conclusions:
- Tau alternative splicing is differentially regulated in the PNS.
- Specific tau isoforms, especially HMW-3R-tau, play a critical role in promoting axonal growth and regeneration in the PNS.
- Findings offer insights into potential therapeutic targets for peripheral nerve repair.
