KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS

Authors

Akintomide Apara, Bascom Palmer Eye Institute
Joana Galvao, Shiley Eye Center, University of California San Diego
Yan Wang, Interdisciplinary Stem Cell Institute
Murray G. Blackmore, Marquette UniversityFollow
Allison Trillo, Bascom Palmer Eye Institute
Keiichiro Iwao, Bascom Palmer Eye Institute
Dale P. Brown Jr., Bascom Palmer Eye Institute
Kimberly A. Fernandes, Flaum Eye Institute, University of Rochester Medical Center
Abigail Huang, Shiley Eye Center, University of California San Diego
Tu Nguyen, Shiley Eye Center, University of California San Diego
Masoumeh Ashouri, Shiley Eye Center, University of California San Diego
Ziong Zhang, Shiley Eye Center, University of California San Diego
Peter S. Shaw, Shiley Eye Center, University of California San Diego
Noelia J. Kunzevitzky, Bascom Palmer Eye Institute
Darcie L. Moore, Bascom Palmer Eye Institute
Richard T. Libby, Flaum Eye Institute, University of Rochester Medical Center
Jeffrey L. Goldberg, Bascom Palmer Eye Institute

Document Type

Article

Language

eng

Publication Date

10-4-2017

Publisher

Society of Neuroscience

Source Publication

Journal of Neuroscience

Source ISSN

0270-6474

Abstract

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9's axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9's neurite growth suppression in vitro and promoted axon regeneration in vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.

Comments

Published version. Journal of Neuroscience, Vol. 37, No. 40 (October 4, 2017): 9632-9644. DOI. ©2017 the authors. Used with permission.

Recommended Citation

Apara, Akintomide; Galvao, Joana; Wang, Yan; Blackmore, Murray G.; Trillo, Allison; Iwao, Keiichiro; Brown, Dale P. Jr.; Fernandes, Kimberly A.; Huang, Abigail; Nguyen, Tu; Ashouri, Masoumeh; Zhang, Ziong; Shaw, Peter S.; Kunzevitzky, Noelia J.; Moore, Darcie L.; Libby, Richard T.; and Goldberg, Jeffrey L., "KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS" (2017). Biological Sciences Faculty Research and Publications. 616.
https://epublications.marquette.edu/bio_fac/616