PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons

被引：8

作者：

Alber, Stefanie ^{[1
,2
,9
]}

Di Matteo, Pierluigi ^{[1
,2
]}

Zdradzinski, Matthew D. ^{[3
]}

Dalla Costa, Irene ^{[3
]}

Medzihradszky, Katalin F. ^{[4
]}

Kawaguchi, Riki ^{[5
,6
]}

Di Pizio, Agostina ^{[1
,2
]}

Freund, Philip ^{[1
,2
]}

Panayotis, Nicolas ^{[1
,2
]}

Marvaldi, Letizia ^{[1
,2
,7
]}

Doron-Mandel, Ella ^{[1
,2
]}

Okladnikov, Nataliya ^{[1
,2
]}

Rishal, Ida ^{[1
,2
]}

Nevo, Reinat ^{[8
]}

Coppola, Giovanni ^{[5
,6
,10
]}

Lee, Seung Joon ^{[3
,11
]}

Sahoo, Pabitra K. ^{[3
]}

Burlingame, Alma L. ^{[4
]}

Twiss, Jeffery L. ^{[3
]}

Fainzilber, Mike ^{[1
,2
]}

机构：

[1] Weizmann Inst Sci, Dept Biomol Sci & Mol Neurosci, IL-7610001 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Mol Neurosci, IL-7610001 Rehovot, Israel

[3] Univ South Carolina, Dept Biol Sci, Columbia, SC 29208 USA

[4] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA

[5] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Neurol, Los Angeles, CA 90095 USA

[7] Univ Turin, Neurosci Inst Cavalieri Ottolenghi, Dept Neurosci Rita Levi Montalcini, I-10043 Orbassano, Italy

[8] Weizmann Inst Sci, Dept Biomol Sci, IL-7610001 Rehovot, Israel

[9] Roche Neurosci, CH-4070 Basel, Switzerland

[10] Regeneron Pharmaceut, Tarrytown, NY 10591 USA

[11] Biogen, Cambridge, MA 02142 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 30期

关键词：

TRACT-BINDING-PROTEIN; LOCAL TRANSLATION; RNA; CONVERSION; GROWTH; INHIBITION; EXPRESSION; PROMOTE; DISEASE; DESIGN;

D O I：

10.1126/sciadv.adi0286

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 ss 1 (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.

引用

页数：20

共 72 条

[1] A Role for Polypyrimidine Tract Binding Protein in the Establishment of Focal Adhesions [J].