Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin
Melinda S. Beccari, Olatz Arnold-García, 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, Carlos Castillo-Rangel, Dong Hyun Kim, Ze’ev Melamed, Cathleen Lutz, Clotilde Lagier‐Tourenne, Kevin D. Corbett, Jone López‐Erauskin, Don W. Cleveland
Abstract
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.