Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways
| Autor: | Nina Irwin, Mariko L Howe, Barbara Lorber, Larry I. Benowitz |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Central Nervous System
Male Nervous system Green Fluorescent Proteins Protein Serine-Threonine Kinases Biology Retinal ganglion Article Retina Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Dorsal root ganglion Tubulin Ganglia Spinal medicine Animals RNA Antisense Peripheral Nerves Axon Spinal Cord Injuries 030304 developmental biology Neurons 0303 health sciences General Neuroscience Regeneration (biology) Calcium-Binding Proteins Rats Inbred F344 Oligodendrocyte Nerve Regeneration Rats Disease Models Animal medicine.anatomical_structure Gene Expression Regulation nervous system Optic Nerve Injuries Intercellular Signaling Peptides and Proteins sense organs Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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