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Nat Commun. 2018 Aug 22;9(1):3358. doi: 10.1038/s41467-018-05647-x.

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

Author information

1
Department of Biological Sciences, University of South Carolina, Columbia, 29208, SC, USA.
2
Department of Cell Biology, Emory University College of Medicine, Atlanta, 30322, GA, USA.
3
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 76100, Israel.
4
FM Kirby Neurobiology Center and Boston Children's Hospital and Harvard Medical School, Boston, 02115, MA, USA.
5
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, 94158, CA, USA.
6
Department of Statistics, University of South Carolina, Columbia, 29208, SC, USA.
7
Department of Biological Sciences, University of South Carolina, Columbia, 29208, SC, USA. twiss@mailbox.sc.edu.

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.

PMID:
30135423
PMCID:
PMC6105716
DOI:
10.1038/s41467-018-05647-x
[Indexed for MEDLINE]
Free PMC Article

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