Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin

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 wildtype 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 a/b 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.