Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways.
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.
Lorber
Barbara
B
Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachusetts, USA.
Howe
Mariko L
ML
Benowitz
Larry I
LI
Irwin
Nina
N
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000503:physiopathology*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010525:Peripheral Nerves / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014404:Tubulin / Q000378:metabolism
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016372:RNA, Antisense; D014404:Tubulin; C462941:beta3 tubulin, mouse; C485184:enhanced green fluorescent protein; C034733:oncomodulin; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases