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

• DOI: 10.1038/s41467-018-05647-x
• Publication Date: 2018-08-16T12:02:47Z
• Authors: Pabitra K. Sahoo; Seung Joon Lee; Poonam B. Jaiswal; Stefanie Alber; Amar N. Kar; Sharmina Miller-R...; Elizabeth E. Taylor; Terika Smith; Bhagat Singh; Tammy Szu-Yu Ho; Anatoly Urisman; Shreya Chand; Edsel A. Pena; Alma L. Burlingame; Clifford J. Woolf; Mike Fainzilber; Arthur W. English; Jeffery L. Twiss
• Keywords: Male; Cells; 1.1 Normal biological development and functioning; Science; Messenger; Neurodegenerative; Regenerative Medicine; Cytoplasmic Granules; Fluorescence; Article; Rats, Sprague-Dawley; Mice; 03 medical and health sciences; Underpinning research; Genetics; Animals; Humans; RNA, Messenger; Poly-ADP-Ribose Binding Proteins; Peripheral Neuropathy; Cells, Cultured; Microscopy; 0303 health sciences; Cultured; Q; Neurosciences; Axons; Nerve Regeneration; Rats; HEK293 Cells; Microscopy, Fluorescence; Neurological; NIH 3T3 Cells; RNA; Female; Sprague-Dawley; Fluorescence Recovery After Photobleaching

AbstractCritical 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.