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.

Details

Title
Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration
Author
Sahoo, Pabitra K 1   VIAFID ORCID Logo  ; Lee, Seung Joon 1 ; Jaiswal, Poonam B 2 ; Alber, Stefanie 3 ; Kar, Amar N 1 ; Miller-Randolph, Sharmina 1 ; Taylor, Elizabeth E 1 ; Smith, Terika 1 ; Singh, Bhagat 4 ; Tammy Szu-Yu Ho 4 ; Urisman, Anatoly 5   VIAFID ORCID Logo  ; Chand, Shreya 5 ; Pena, Edsel A 6 ; Burlingame, Alma L 5 ; Woolf, Clifford J 4   VIAFID ORCID Logo  ; Fainzilber, Mike 3   VIAFID ORCID Logo  ; English, Arthur W 2 ; Twiss, Jeffery L 1   VIAFID ORCID Logo 

1  Department of Biological Sciences, University of South Carolina, Columbia, SC, USA 
2  Department of Cell Biology, Emory University College of Medicine, Atlanta, GA, USA 
3  Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel 
4  FM Kirby Neurobiology Center and Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA 
5  Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA 
6  Department of Statistics, University of South Carolina, Columbia, SC, USA 
Pages
1-14
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05647-x
ProQuest document ID
2091744447
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.