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Author Notes:

Correspondence and requests for materials should be addressed to J.L.T. (email: twiss@mailbox.sc.edu)

P.K.S., A.W.E. and J.L.T. designed the study.

Experiments were performed by P.K.S., S.J.L., P.B.J., S.A., A.N.K., S.M.R., T.S., B.S., E.E.T., T.S.H. and A.U., A.L.B., C.J.W., M.F., and A.W.E. provided critical reagents, advanced instrumentation, experimental models, and expert guidance.

E.A.P. provided statistical analyses.

J.L.T. and P.K.S. wrote the manuscript.

All authors commented on the manuscript draft and approved the final version.

The Histochemistry and Tissue Processing Core of Nemours/Alfred I. duPont Hospital performed tissue processing for Children.

M.F. is the incumbent of the Chaya Professorial Chair in Molecular Neuroscience at the Weizmann Institute of Science, and J.L.T. is the incumbent of the SmartState Chair in Childhood Neurotherapeutics at the University of South Carolina.

The authors declare no competing interests.

Subjects:

Research Funding:

This work was supported by grant funds from National Institutes of Health (R01-NS041596 and R01-NS089633 to J.L.T. and NS057190 to A.W.E.), Department of Defense—Congressionally Mandated Research Program (W81XWH-2013-1-308 OR120042 to J.L.T. and M.F.), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to A.L.B., C.J.W., J.L.T., and M.F.).

MS experiments were performed at the Biomedical Mass Spectrometry Resource at UCSF supported by funding from the Howard Hughes Medical Institute (to A.L.B.).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • ENDORIBONUCLEASE G3BP
  • LOCAL TRANSLATION
  • SENSORY NEURONS
  • DISTINCT MODES
  • UTR ELEMENTS
  • GROWTH
  • INJURY
  • LOCALIZATION
  • DYNAMICS
  • BINDING

Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration

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Journal Title:

Nature Communications

Volume:

Volume 9, Number 1

Publisher:

, Pages 3358-3358

Type of Work:

Article | Final Publisher PDF

Abstract:

Critical functions of intra-axonally synthesized proteins are thought to depend on regulated recruitment of mRNA from storage depots in axons. Here we show that axotomy of mammalian neurons induces translation of stored axonal mRNAs via regulation of the stress granule protein G3BP1, to support regeneration of peripheral nerves. G3BP1 aggregates within peripheral nerve axons in stress granule-like structures that decrease during regeneration, with a commensurate increase in phosphorylated G3BP1. Colocalization of G3BP1 with axonal mRNAs is also correlated with the growth state of the neuron. Disrupting G3BP functions by overexpressing a dominant-negative protein activates intra-axonal mRNA translation, increases axon growth in cultured neurons, disassembles axonal stress granule-like structures, and accelerates rat nerve regeneration in vivo.

Copyright information:

© 2018, The Author(s)

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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