Journal article
Disruption of G3BP1 granules promotes mammalian CNS and PNS axon regeneration
Proceedings of the National Academy of Sciences - PNAS, v 122(9), e2411811122
04 Mar 2025
PMID: 40014573
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in
, increases the growth of spontaneously regenerating axons. Inhibition of G3BP1 by expression of its acidic or "B-domain" accelerates axon regeneration after nerve injury, bringing a potential therapeutic strategy for peripheral nerve repair. Here, we asked whether G3BP1 inhibition is a viable strategy to promote regeneration in injured mammalian central nervous system (CNS) where axons do not regenerate spontaneously. G3BP1 B-domain expression was found to promote axon regeneration in the transected spinal cord provided with a permissive peripheral nerve graft (PNG) as well as in crushed optic nerve. Moreover, a cell-permeable peptide (CPP) to a subregion of B-domain (rodent G3BP1 amino acids 190 to 208) accelerated axon regeneration after peripheral nerve injury and promoted regrowth of reticulospinal axons into the distal transected spinal cord through a bridging PNG. G3BP1 CPP promoted axon growth from rodent and human neurons cultured on permissive substrates, and this function required alternating Glu/Asp-Pro repeats that impart a unique predicted tertiary structure. The G3BP1 CPP disassembles axonal G3BP1, G3BP2, and FMRP, but not FXR1, granules and selectively increases axonal protein synthesis in cortical neurons. These studies identify G3BP1 granules as a key regulator of axon growth in CNS neurons and demonstrate that disassembly of these granules promotes retinal axon regeneration in injured optic nerve and reticulospinal axon elongation into permissive environments after CNS injury. This work highlights G3BP1 granule disassembly as a potential therapeutic strategy for enhancing axon growth and neural repair.
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Details
- Title
- Disruption of G3BP1 granules promotes mammalian CNS and PNS axon regeneration
- Creators
- Pabitra K Sahoo - University of South CarolinaManasi Agrawal - University of South CarolinaNicholas Hanovice - Boston Children's HospitalPatricia J Ward - Emory UniversityMeghal Desai - RütgersTerika P Smith - University of South CarolinaHaoMin SiMa - Boston Children's HospitalJennifer N Dulin - Texas A&M UniversityLauren S Vaughn - University of South CarolinaMark H Tuszynski - University of California, San DiegoKristy Welshhans - University of South CarolinaLarry I Benowitz - Boston Children's HospitalArthur W English - Emory UniversityJohn D Houle - Drexel UniversityJeffery L Twiss - University of South Carolina
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 122(9), e2411811122
- Publisher
- PNAS
- Number of pages
- 12
- Grant note
- N/A / South Carolina Spinal Cord Injury Research Fund (SCIRF) R01-NS0117821 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) N/A / Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF) 733151 / George W. Neilson Foundation N/A / Merkin Peripheral Neuropathy and Nerve Regeneration Center N/A / University of South Carolina Vice President for Research Office
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001449356300001
- Scopus ID
- 2-s2.0-86000040885
- Other Identifier
- 991022032773304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences