@article{efd2b20f217d44dfa7c7549a836abfe9,
title = "Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System",
abstract = "Signal transducer and activator of transcription 3 (STAT3) is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature CNS neurons remain unclear. Here, we show that along with nuclear translocation, STAT3 translocates to mitochondria in mature CNS neurons upon cytokine stimulation. Loss- and gain-of-function studies using knockout mice and viral expression of various STAT3 mutants demonstrate that STAT3's transcriptional function is indispensable for CNS axon regrowth, whereas mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth. STAT3's localization, functions, and growth-promoting effects are regulated by mitogen-activated protein kinase kinase (MEK), an effect further enhanced by Pten deletion, leading to extensive axon regrowth in the mouse optic pathway and spinal cord. These results highlight CNS neuronal dependence on STAT3 transcriptional activity, with mitochondrial STAT3 providing ancillary roles, and illustrate a critical contribution for MEK in enhancing diverse STAT3 functions and axon regrowth.",
author = "Xueting Luo and Marcio Ribeiro and Bray, {Eric R.} and Lee, {Do Hun} and Yungher, {Benjamin J.} and Mehta, {Saloni T.} and Thakor, {Kinjal A.} and Francisca Diaz and Lee, {Jae K.} and Moraes, {Carlos T.} and Bixby, {John L.} and Lemmon, {Vance P.} and Park, {Kevin K.}",
note = "Funding Information: This work was supported by grants from the National Eye Institute (NEI) 1R01EY022961-01 (to K.K.P.), National Institute of Neurological Disorders and Stroke (NINDS) R01NS009923-43 (to K.K.P.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD057632 (to V.P.L. and J.L.B.), 5R01EY010804 (to C.T.M.), 5R01NS079965 (to C.T.M.), U.S. Army W81XWH-05-1-0061 (to K.K.P.), W81XWH-12-1-0319 (to K.K.P.), Ziegler Foundation (to K.K.P.), Pew Charitable Trust (to K.K.P.), Craig H. Neilsen Foundation (to K.K.P.), and the Buoniconti Fund (to K.K.P., V.P.L., J.K.L., and J.L.B.). We thank Aline-Ohashi Hida for her help with Cox10 f/f mice, Melissa Carballosa-Gautam at the Miami Project to Cure Paralysis Imaging Core, Margaret Rebecca Bates and Vania Wolff Almeida at the University of Miami Electron Microscopy Core, Yadira Salgueiro in the K.K.P. lab and Pingping Jia at the University of Miami Viral Vector Core. Funding Information: This work was supported by grants from the National Eye Institute (NEI) 1R01EY022961-01 (to K.K.P.), National Institute of Neurological Disorders and Stroke (NINDS) R01NS009923-43 (to K.K.P.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD057632 (to V.P.L. and J.L.B.), 5R01EY010804 (to C.T.M.), 5R01NS079965 (to C.T.M.), U.S. Army W81XWH-05-1-0061 (to K.K.P.), W81XWH-12-1-0319 (to K.K.P.), Ziegler Foundation (to K.K.P.), Pew Charitable Trust (to K.K.P.), Craig H. Neilsen Foundation (to K.K.P.), and the Buoniconti Fund (to K.K.P., V.P.L., J.K.L., and J.L.B.). We thank Aline-Ohashi Hida for her help with Cox10f/f mice, Melissa Carballosa-Gautam at the Miami Project to Cure Paralysis Imaging Core, Margaret Rebecca Bates and Vania Wolff Almeida at the University of Miami Electron Microscopy Core, Yadira Salgueiro in the K.K.P. lab and Pingping Jia at the University of Miami Viral Vector Core. Publisher Copyright: {\textcopyright} 2016 The Authors.",
year = "2016",
month = apr,
day = "12",
doi = "10.1016/j.celrep.2016.03.029",
language = "English",
volume = "15",
pages = "398--410",
journal = "Cell Reports",
issn = "2211-1247",
number = "2",
}