PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons.
PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons.
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DOI：
10.1126/sciadv.adi0286
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发表时间：
2023-07-28
期刊：
影响因子：
13.6
通讯作者：
Fainzilber, Mike
中科院分区：
文献类型：
--
作者：
Alber, Stefanie;Di Matteo, Pierluigi;Zdradzinski, Matthew D.;Dalla Costa, Irene;Medzihradszky, Katalin F.;Kawaguchi, Riki;Di Pizio, Agostina;Freund, Philip;Panayotis, Nicolas;Marvaldi, Letizia;Doron-Mandel, Ella;Okladnikov, Nataliya;Rishal, Ida;Nevo, Reinat;Coppola, Giovanni;Lee, Seung Joon;Sahoo, Pabitra K.;Burlingame, Alma L.;Twiss, Jeffery L.;Fainzilber, Mike
多聚嘧啶束结合蛋白1（PTBP1）被认为只在胚胎阶段的中枢神经元中表达。它的下调触发前体和非神经元细胞中的神经元分化，这是最近测试的一种用于从头产生神经元以改善神经退行性疾病的方法。此外，在成熟的中枢神经元中，PTBP 1被其副产物PTBP 2取代。出乎意料的是，我们发现这两种蛋白质在成人感觉和运动神经元中共表达，PTBP2主要局限于细胞核，而PTBP1也显示轴突定位。外周神经损伤后，轴突PTBP 1表达水平显著升高，并与参与损伤反应和神经再生的mRNA（包括输入素β1（KPNB 1）和RHOA）相关。PTBP1的扰动影响轴突的局部翻译、伤害感受器神经元再生以及热感觉和机械感觉。因此，PTBP1在成人轴突中具有功能性作用。因此，在考虑将PTBP1靶向用于治疗目的之前需要谨慎。PTBP1在成人感觉轴突的翻译和感觉中发挥作用，将其作用扩展到胚胎神经元发育之外。
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. PTBP1 functions in translation and sensation in adult sensory axons, expanding its roles beyond embryonic neuron development.
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