Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin
Stathmin-2 (also known as <i>SCG10</i>) is encoded by the <i>STMN2</i> gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced and polyadenylated in motor neurons, a pathogenic consequence of nuclear loss of function of the RNA binding protein TDP-43. While stathmin-2 has been shown to enhance regeneration after axonal injury to axons of cultured motor neurons, here, we show that after crush injury within the adult murine nervous system of wild-type or stathmin-2-null mice, the presence of stathmin-2 reduces axonal and neuromuscular junction degeneration and stimulates reinnervation and functional recovery. Mechanistically, although stathmin-2 has been proposed to function through direct binding to α/β tubulin heterodimers and correspondingly to affect microtubule assembly and dynamics, stathmin-2's role in axon regeneration after axotomy is shown to be independent of its tubulin binding abilities.
Authors
- Olatz Arnold-García (ORCID: https://orcid.org/0000-0003-3312-4790)
- Melinda S. Beccari (ORCID: https://orcid.org/0000-0003-1019-6388)
- Jone López‐Erauskin (ORCID: https://orcid.org/0009-0000-7570-7180)
- Ze’ev Melamed (ORCID: https://orcid.org/0000-0002-3734-3926)
- Kevin D. Corbett (ORCID: https://orcid.org/0000-0001-5854-2388)
- Don W. Cleveland (ORCID: https://orcid.org/0000-0002-1934-3682)
- Jonathan W. Artates
- Michael W. Baughn (ORCID: https://orcid.org/0000-0001-8525-8024)
- Cathleen M. Lutz (ORCID: https://orcid.org/0000-0003-2502-1900)
- Carlos Castillo-Rangel (ORCID: https://orcid.org/0000-0003-2956-5112)
- Melissa McAlonis‐Downes (ORCID: https://orcid.org/0000-0002-8152-2075)
- Clotilde Lagier‐Tourenne (ORCID: https://orcid.org/0000-0002-3058-8322)
- Dong Hyun Kim (ORCID: https://orcid.org/0000-0002-8762-1496)
- Jaisen Lim
- Carol N. Bernal-Buenrostro
- Brian Murgia-Bay
- Dulce Fernanda Leyva-Cázares
- Hugo Isaac Rubio-Lara
- Andrea Ramirez-Rodriguez
Institutions
- Broad Institute (US)
- Harvard University (US)
- Hebrew University of Jerusalem (IL)
- Instituto de Salud Carlos III (ES)
- University of California San Diego (US)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Massachusetts General Hospital (US)
- Centro de Investigación Biomédica en Red (ES)
- Jackson Laboratory (US)
- Princess Máxima Center (NL)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-05-20
- DOI
- https://doi.org/10.1073/pnas.2502294122
- Citations
- 13
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 18.06
Funders
- Muscular Dystrophy Association
- NOMIS Stiftung
- National Institute on Aging
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke