The small GTPase CDC42 promotes axon growth through actin filament polymerization and this growth is driven by axonal localization of the mRNA encoding the prenylated CDC42 isoform (). Here, we show that axonal mRNA transport and translation are decreased by growth-inhibiting stimulation and increased by growth-promoting stimulation. In contrast, axonal mRNA transport and translation are increased by growth inhibition but unaffected by growth promotion. Localized increase in KHSRP in response to growth inhibitory stimulation, through elevation of intracellular Ca, promotes decay of axonal mRNA. Distinct 3'UTR motifs regulate transport and stability of axonal mRNA. KHSRP protein binds to a mRNA motif within nt 801-875 and the mRNA is remarkably increased in axons of mice. Selective depletion of mRNA from axons reverses the accelerated axon regeneration seen in mice.
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| http://dx.doi.org/10.1101/2025.02.06.636857 | DOI Listing |
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