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Targeting Stress Granules to Accelerate Nerve Regeneration

EVENT: 
Lecture
Who Should Attend: 
Researchers

Speakers

Abstract 

Peripheral nerves spontaneously regenerate after injury but injured spinal cord axons have much lower regeneration capacity. Proteins synthesized locally in axons are needed for peripheral nerve regeneration, and several lines of evidence indicate that injured spinal cord axons have the ability to synthesize proteins when they are made competent to regenerate. We recently published work showing that Stress Granules (SGs) serve as mRNA storage sites in axons through aggregation of the SG protein G3BP1. Axonal SGs attenuate axonal protein synthesis and slow axon growth. We developed viral-based (AAV-G3BP1 B domain) and cell permeable peptide-based (190-208 G3BP1 peptide) strategies to cause axonal SG disassembly, and these approaches accelerate PNS axon regeneration. Our preliminary data show high promise for the SG disassembly approach increasing spinal cord axon regeneration under some settings. Indeed, inhibition of G3BP1 accelerates growth of severed reticulospinal axons in peripheral nerve grafts (PNGs) and shows growth promoting effects in transected CST axons. We also uncovered an endogenous pathway that sensory neurons use for disassembling axonal SGs. Specifically, Casein Kinase 2 (CK2) dependent phosphorylation of axonal G3BP1 triggers disassembly of axonal SGs, releasing axonal mRNAs for translation and increasing axon growth. Temporal and spatial specificity of CK2 in axons is driven by translational regulation of its mRNA (Csnk2a1) in axons after injury.

Dr. Sahoo's Figure

Publications

Sahoo PK, Lee SJ, Jaiswal PB, Alber S, Kar AN, Miller-Randolph S, Taylor EE, Smith T, Singh B, Ho TS, Urisman A, Chand S, Pena EA, Burlingame AL, Woolf CJ, Fainzilber M, English AW, Twiss JL.
Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration.
Nat Commun. 2018 Aug 22;9(1):3358. doi: 10.1038/s41467-018-05647-x.
P.K. Sahoo, A.N. Kar, S.J. Lee, S.M. Randolph, M. Terenzio, N. Samra, P. Patel, E. Thames, B. Jones, M. Fainzilber, J.L. Twiss
Disassembly of Axonal G3BP1 Aggregates by a Casein Kinase 2α mRNA Translational Switch
Manuscript under review in Current Biology
Sahoo PK, Murawala P, Sawale PT, Sahoo MR, Tripathi MM, Gaikwad SR, Seshadri V, Joseph J.
Wnt signalling antagonizes stress granule assembly through a Dishevelled-dependent mechanism.
Biol Open. 2012 Feb 15;1(2):109-19. doi: 10.1242/bio.2011023. Epub 2011 Nov 18.

When

Friday, February 7, 2020 - 12:00pm

Where

785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

More Information

Darlene White

Research Methods