Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways.

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Lorber B,Howe ML,Benowitz LI,Irwin N

doi

10.1038/nn.2414

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1407-14

issue

11

eissn

1097-6256

issn

1546-1726

pii

nn.2414

journal_volume

12

pub_type

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