PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons

Stefanie Alber; Pierluigi Di Matteo; Matthew D. Zdradzinski; Irene Dalla Costa; Katalin F. Medzihradszky; Riki Kawaguchi; Agostina Di Pizio; Philip Freund; Nicolas Panayotis; Letizia Marvaldi; Ella Doron-Mandel; Nataliya Okladnikov; Ida Rishal; Reinat Nevo; Giovanni Coppola; Seung Joon Lee; Pabitra K. Sahoo; Alma L. Burlingame; Jeffery L. Twiss; Mike Fainzilber

doi:10.1126/sciadv.adi0286

PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons

Stefanie Alber, Pierluigi Di Matteo, Matthew D. Zdradzinski, Irene Dalla Costa, Katalin F. Medzihradszky, Riki Kawaguchi, Agostina Di Pizio, Philip Freund, Nicolas Panayotis, Letizia Marvaldi, Ella Doron-Mandel, Nataliya Okladnikov, Ida Rishal, Reinat Nevo, Giovanni Coppola, Seung Joon Lee, Pabitra K. Sahoo, Alma L. Burlingame, Jeffery L. Twiss, Mike Fainzilber^*

^*Corresponding author for this work

Department of Biomolecular Sciences

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Polypyrimidine tract binding protein 1 (PTBP1) is thought to be expressed only at embryonic stages in central neurons. Its down-regulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently tested for generation of neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Unexpectedly, we found that both proteins are coexpressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 also shows axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and it associates in axons with mRNAs involved in injury responses and nerve regeneration, including importin β1 (KPNB1) and RHOA. Perturbation of PTBP1 affects local translation in axons, nociceptor neuron regeneration and both thermal and mechanical sensation. Thus, PTBP1 has functional roles in adult axons. Hence, caution is required before considering targeting of PTBP1 for therapeutic purposes.

Original language	English
Article number	adi0286
Journal	Science advances
Volume	9
Issue number	30
DOIs	https://doi.org/10.1126/sciadv.adi0286
Publication status	Published - Jul 2023

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Alber, S., Di Matteo, P., Zdradzinski, M. D., Costa, I. D., Medzihradszky, K. F., Kawaguchi, R., Di Pizio, A., Freund, P., Panayotis, N., Marvaldi, L., Doron-Mandel, E., Okladnikov, N., Rishal, I., Nevo, R., Coppola, G., Joon Lee, S., Sahoo, P. K., Burlingame, A. L., Twiss, J. L., & Fainzilber, M. (2023). PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons. Science advances, 9(30), Article adi0286. https://doi.org/10.1126/sciadv.adi0286

@article{437d9662ac9144fbad4e8830aae0cf45,

title = "PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons",

abstract = "Polypyrimidine tract binding protein 1 (PTBP1) is thought to be expressed only at embryonic stages in central neurons. Its down-regulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently tested for generation of neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Unexpectedly, we found that both proteins are coexpressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 also shows axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and it associates in axons with mRNAs involved in injury responses and nerve regeneration, including importin β1 (KPNB1) and RHOA. Perturbation of PTBP1 affects local translation in axons, nociceptor neuron regeneration and both thermal and mechanical sensation. Thus, PTBP1 has functional roles in adult axons. Hence, caution is required before considering targeting of PTBP1 for therapeutic purposes.",

author = "Stefanie Alber and {Di Matteo}, Pierluigi and Zdradzinski, {Matthew D.} and Costa, {Irene Dalla} and Medzihradszky, {Katalin F.} and Riki Kawaguchi and {Di Pizio}, Agostina and Philip Freund and Nicolas Panayotis and Letizia Marvaldi and Ella Doron-Mandel and Nataliya Okladnikov and Ida Rishal and Reinat Nevo and Giovanni Coppola and {Joon Lee}, Seung and Sahoo, {Pabitra K.} and Burlingame, {Alma L.} and Twiss, {Jeffery L.} and Mike Fainzilber",

year = "2023",

month = jul,

doi = "10.1126/sciadv.adi0286",

language = "English",

volume = "9",

journal = "Science advances",

issn = "2375-2548",

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Alber, S, Di Matteo, P, Zdradzinski, MD, Costa, ID, Medzihradszky, KF, Kawaguchi, R, Di Pizio, A, Freund, P, Panayotis, N, Marvaldi, L, Doron-Mandel, E, Okladnikov, N, Rishal, I, Nevo, R, Coppola, G, Joon Lee, S, Sahoo, PK, Burlingame, AL, Twiss, JL & Fainzilber, M 2023, 'PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons', Science advances, vol. 9, no. 30, adi0286. https://doi.org/10.1126/sciadv.adi0286

TY - JOUR

T1 - PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons

AU - Alber, Stefanie

AU - Di Matteo, Pierluigi

AU - Zdradzinski, Matthew D.

AU - Costa, Irene Dalla

AU - Medzihradszky, Katalin F.

AU - Kawaguchi, Riki

AU - Di Pizio, Agostina

AU - Freund, Philip

AU - Panayotis, Nicolas

AU - Marvaldi, Letizia

AU - Doron-Mandel, Ella

AU - Okladnikov, Nataliya

AU - Rishal, Ida

AU - Nevo, Reinat

AU - Coppola, Giovanni

AU - Joon Lee, Seung

AU - Sahoo, Pabitra K.

AU - Burlingame, Alma L.

AU - Twiss, Jeffery L.

AU - Fainzilber, Mike

PY - 2023/7

Y1 - 2023/7

N2 - Polypyrimidine tract binding protein 1 (PTBP1) is thought to be expressed only at embryonic stages in central neurons. Its down-regulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently tested for generation of neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Unexpectedly, we found that both proteins are coexpressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 also shows axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and it associates in axons with mRNAs involved in injury responses and nerve regeneration, including importin β1 (KPNB1) and RHOA. Perturbation of PTBP1 affects local translation in axons, nociceptor neuron regeneration and both thermal and mechanical sensation. Thus, PTBP1 has functional roles in adult axons. Hence, caution is required before considering targeting of PTBP1 for therapeutic purposes.

AB - Polypyrimidine tract binding protein 1 (PTBP1) is thought to be expressed only at embryonic stages in central neurons. Its down-regulation triggers neuronal differentiation in precursor and non-neuronal cells, an approach recently tested for generation of neurons de novo for amelioration of neurodegenerative disorders. Moreover, PTBP1 is replaced by its paralog PTBP2 in mature central neurons. Unexpectedly, we found that both proteins are coexpressed in adult sensory and motor neurons, with PTBP2 restricted mainly to the nucleus, while PTBP1 also shows axonal localization. Levels of axonal PTBP1 increased markedly after peripheral nerve injury, and it associates in axons with mRNAs involved in injury responses and nerve regeneration, including importin β1 (KPNB1) and RHOA. Perturbation of PTBP1 affects local translation in axons, nociceptor neuron regeneration and both thermal and mechanical sensation. Thus, PTBP1 has functional roles in adult axons. Hence, caution is required before considering targeting of PTBP1 for therapeutic purposes.

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U2 - 10.1126/sciadv.adi0286

DO - 10.1126/sciadv.adi0286

M3 - Article

C2 - 37506203

AN - SCOPUS:85165940241

SN - 2375-2548

VL - 9

JO - Science advances

JF - Science advances

IS - 30

M1 - adi0286

ER -

PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons

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