PTBP1 Regulates Injury Responses and Sensory Pathways in Adult Peripheral Neurons

Alber, S.; Di-Matteo, P.; Zdradzinski, M. D.; Marvaldi, L.; Kawaguchi, R.; Medzihradszky, K. F.; Doron-Mandel, E.; Okladnikov, N.; Rishal, I.; Nevo, R.; Lee, S. J.; Sahoo, P. K.; Burlingame, A. L.; Coppola, G.; Twiss, J. L.; Fainzilber, M.

doi:10.1101/2020.10.22.348631

bioRxiv · 10.1101/2020.10.22.348631

PTBP1 Regulates Injury Responses and Sensory Pathways in Adult Peripheral Neurons

Alber, S.·Di-Matteo, P.·Zdradzinski, M. D.·Marvaldi, L.·Kawaguchi, R.·Medzihradszky, K. F.·Doron-Mandel, E.·Okladnikov, N.·Rishal, I.·Nevo, R.·Lee, S. J.·Sahoo, P. K.·Burlingame, A. L.·Coppola, G.·Twiss, J. L.·Fainzilber, M.

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Abstract

Polypyrimidine Tract Binding Protein 1 (PTBP1) is expressed only at embryonic stages in central neurons. Its downregulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently used to generate neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Surprisingly, we found both proteins co-expressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 shows strong axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and its cargos include mRNAs involved in axonal growth and regeneration, such as importin {beta}1 and RhoA. Perturbation of PTBP1 affects neuronal injury responses, axon outgrowth and sensation in vivo. Thus, PTBP1 has roles in sensory function and regenerative capacity of adult sensory neurons. These findings suggest that caution may be required before considering targeting PTBP1 for therapeutic purposes.

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Alber, S., Di-Matteo, P., Zdradzinski, M. D., Marvaldi, L., Kawaguchi, R., Medzihradszky, K. F., Doron-Mandel, E., Okladnikov, N., Rishal, I., Nevo, R., Lee, S. J., Sahoo, P. K., Burlingame, A. L., Coppola, G., Twiss, J. L., Fainzilber, M.. 2020-10-22. PTBP1 Regulates Injury Responses and Sensory Pathways in Adult Peripheral Neurons. https://doi.org/10.1101/2020.10.22.348631

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