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

• 成果类型: Article
• 署名作者: Beccari, Melinda S.; Arnold-Garcia, Olatz; Baughn, Michael W.; Artates, Jonathan W.; McAlonis-Downes, Melissa; Lim, Jaisen; Leyva-Cazares, Dulce Fernanda; Rubio-Lara, Hugo Isaac; Ramirez-Rodriguez, Andrea; Bernal-Buenrostro, Carol N.; Murgia-Bay, Brian; Rangel, Carolina K.; Kim, Dong Hyun; Melamed, Ze'ev; Lutz, Cathleen M.; Lagier-Tourenne, Clotilde; Corbett, Kevin D.; Lopez-Erauskin, Jone; Cleveland, Don W.
• 署名单位: University of California System; University of California San Diego; Instituto de Investigacion Sanitaria Biogipuzkoa; CIBERNED; Universidad Autonoma de Baja California; Hebrew University of Jerusalem; Jackson Laboratory; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; Pfizer; Pfizer USA
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11476
• DOI: 10.1073/pnas.25022941221
• 发表日期: 2025-05-20
• 关键词: frontotemporal lobar degeneration; in-vitro phosphorylation; dna-binding; tdp-43 immunoreactivity; alzheimer-disease; protein 43; identification; GROWTH; cells; scg10

摘要

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 alpha/beta 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.