Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (19)
Melinda S. Beccari
Department of Cellular and Molecular Medicine, University of California, San Diego
Olatz Arnold-Garcia
Department of Cellular and Molecular Medicine, University of California, San Diego
Michael W. Baughn
Department of Cellular and Molecular Medicine, University of California, San Diego
Jonathan W. Artates
Department of Cellular and Molecular Medicine, University of California, San Diego
Melissa McAlonis-Downes
Department of Cellular and Molecular Medicine, University of California, San Diego
Jaisen Lim
Department of Cellular and Molecular Medicine, University of California, San Diego
Dulce Fernanda Leyva-Cázares
Department of Cellular and Molecular Medicine, University of California, San Diego
Hugo Isaac Rubio-Lara
Department of Cellular and Molecular Medicine, University of California, San Diego
Andrea Ramirez-Rodriguez
Department of Cellular and Molecular Medicine, University of California, San Diego
Carol N. Bernal-Buenrostro
Department of Cellular and Molecular Medicine, University of California, San Diego
Brian Murgia-Bay
Department of Cellular and Molecular Medicine, University of California, San Diego
Carolina K. Rangel
Prinses Maxima Centrum voor Kinderoncologie
Dong Hyun Kim
Department of Chemistry
Ze’ev Melamed
Department of Cellular and Molecular Medicine, University of California, San Diego
Cathleen M. Lutz
Rare Disease Translational Center, The Jackson Laboratory
Clotilde Lagier-Tourenne
Department of Neurology, Sean M. Healey and AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School
Kevin D. Corbett
Jone López-Erauskin
Department of Cellular and Molecular Medicine, University of California, San Diego
Don W. Cleveland
Department of Cellular and Molecular Medicine, University of California, San Diego