Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 22, 2018
- Source ID
- 10.1038/s41467-018-05647-x
Entities
People
- Alma L. Burlingame
- Amar N. Kar
- Anatoly Urisman
- Arthur W. English
- Bhagat Singh
- Clifford J. Woolf
- Edsel A. Pena
- Elizabeth E. Taylor
- Jeffery L Twiss
- Mike Fainzilber
- Pabitra K Sahoo
- Poonam B. Jaiswal
- Seung Joon Lee
- Sharmina Miller-randolph
- Shreya Chand
- Stefanie Alber
- Tammy Szu-yu Ho
- Terika Smith
Organizations
- Adelson Foundation
- Congressionally Directed Medical Research Programs
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense