Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin
- Melinda S. Beccari
- Olatz Arnold-Garcia
- Michael W. Baughn
- Jonathan W. Artates
- Melissa McAlonis-Downes
- Jaisen Lim
- Dulce Fernanda Leyva-Cázares
- Hugo Isaac Rubio-Lara
- Andrea Ramirez-Rodriguez
- Carol N. Bernal-Buenrostro
- Brian Murgia-Bay
- Carolina K. Rangel
- Dong Hyun Kim
- Ze’ev Melamed
- Cathleen M. Lutz
- Clotilde Lagier-Tourenne
- Kevin D. Corbett
- Jone López-Erauskin
- Don W. Cleveland
2025-05-20
Stathmin-2 (also known as SCG10 ) is encoded by the STMN2 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.