Document Type
Article
Publication Date
5-27-2025
Original Citation
Beccari M,
Arnold-Garcia O,
Baughn M,
Artates J,
McAlonis-Downes M,
Lim J,
Leyva-Cázares D,
Rubio-Lara H,
Ramirez-Rodriguez A,
Bernal-Buenrostro C,
Murgia-Bay B,
Rangel C,
Kim D,
Melamed Z,
Lutz C,
Lagier-Tourenne C,
Corbett K,
López-Erauskin J,
Cleveland D.
Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin. Proc Natl Acad Sci U S A. 2025;122(21):e2502294122.
Keywords
JMG, Animals, Stathmin, Axons, Motor Neurons, Mice, Tubulin, Nerve Regeneration, Mice, Knockout, Protein Binding, Neuromuscular Junction, Humans, Microtubules
JAX Source
Proc Natl Acad Sci U S A. 2025;122(21):e2502294122.
ISSN
1091-6490
PMID
40392845
DOI
https://doi.org/10.1073/pnas.2502294122
Abstract
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.
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