Article abstract
Nature Neuroscience 12, 1407 - 1414 (2009)
Published online: 25 October 2009 | doi:10.1038/nn.2414
Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways
Barbara Lorber1,2,4, Mariko L Howe1, Larry I Benowitz1,2,3 & Nina Irwin1,2
Abstract
Mammalian sterile 20-like kinase-3b (Mst3b, encoded by Stk24), regulates axon outgrowth in embryonic cortical neurons in culture, but its role in vivo and in neural repair is unknown. Here we show that Mst3b mediates the axon-promoting effects of trophic factors in mature rat retinal ganglion cells (RGCs) and dorsal root ganglion (DRG) neurons, and is essential for axon regeneration in vivo. Reducing Mst3b levels using short hairpin RNA prevented RGCs and DRG neurons from regenerating axons in response to growth factors in culture, as did expression of a kinase-dead Mst3b mutant. Conversely, expression of constitutively active Mst3b enabled both types of neurons to extend axons without growth factors. In vivo, RGCs lacking Mst3b failed to regenerate injured axons when stimulated by intraocular inflammation. DRG neurons regenerating axons in vivo showed elevated Mst3b activity, and reducing Mst3b expression attenuated regeneration and p42/44 MAPK activation. Thus, Mst3b regulates axon regeneration in both CNS and PNS neurons.
- Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts, USA.
- Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
- Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
- Present address: Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Correspondence to: Larry I Benowitz1,2,3 e-mail: larry.benowitz@childrens.harvard.edu
Correspondence to: Nina Irwin1,2 e-mail: nina.irwin@childrens.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
How inflammation promotes regenerationNature Neuroscience News and Views (01 Jun 2006)
Turbocharging neurons for growth: accelerating regeneration in the adult CNSNature Neuroscience News and Views (01 Jan 2001)
See all 4 matches for News And ViewsRESEARCH
Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3BOncogene Original Article
Manganese Superoxide Dismutase Affects Cytochrome c Release and Caspase-9 Activation After Transient Focal Cerebral Ischemia in MiceJournal of Cerebral Blood Flow & Metabolism Original Article
See all 58 matches for Research
