Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Yuichi SekineStephen M Strittmatter

Abstract

After brain or spinal cord trauma, interaction of Nogo-A with neuronal NgR1 limits regenerative axonal sprouting and functional recovery. Cellular signaling by lipid-anchored NgR1 requires a coreceptor but the relevant partner in vivo is not clear. Here, we examined proteins enriched in NgR1 immunoprecipitates by Nogo-A exposure, identifying CRMP2, a cytosolic protein implicated in axon growth inhibition by Semaphorin/Plexin complexes. The Nogo-A-induced association of NgR1 with CRMP2 requires PlexinA2 as a coreceptor. Non-neuronal cells expressing both NgR1 and PlexinA2, but not either protein alone, contract upon Nogo-A exposure. Inhibition of cortical axon regeneration by Nogo-A depends on a NgR1/PlexinA2 genetic interaction because double-heterozygous NgR1+/-, PlexinA2+/- neurons, but not single-heterozygote neurons, are rescued from Nogo-A inhibition. NgR1 and PlexinA2 also interact genetically in vivo to restrict corticospinal sprouting in mouse cervical spinal cord after unilateral pyramidotomy. Greater post-injury sprouting in NgR1+/-, PlexinA2+/- mice supports enhanced neurological recovery of a mixed female and male double-heterozygous cohort. Thus, a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair after adul...Continue Reading

Citations

Nov 22, 2019·The Journal of Biological Chemistry·Yuichi SekineStephen M Strittmatter
Dec 24, 2019·Frontiers in Cellular Neuroscience·Fabio LaredoAndrea Tedeschi
Mar 27, 2020·Frontiers in Neuroscience·Michael J RigbyLuigi Puglielli
Apr 29, 2021·Neural Regeneration Research·Zhi-Sheng JiHong-Sheng Lin
May 25, 2021·Frontiers in Molecular Neuroscience·Camille CuveillierAnnie Andrieux
Dec 4, 2021·ELife·Benoît BoulanJean-Christophe Deloulme

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