Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses

Experimental Neurology
Jun NagaiToshio Ohshima

Abstract

Central nervous system (CNS) regeneration is restricted by both the lack of neurotrophic responses and the presence of inhibitory factors. As of yet, a common mediator of these two pathways has not been identified. Microtubule dynamics is responsible for several key processes after CNS injuries: intracellular trafficking of receptors for neurotrophic factors, axonal retraction by inhibitory factors, and secondary tissue damages by inflammation and scarring. Kinases regulating microtubule organization, such as Cdk5 or GSK3β, may play pivotal roles during CNS recovery, but the molecular mechanisms remain to be elucidated. Collapsin response mediator protein 2 (CRMP2) stabilizes cytoskeletal polymerization, while CRMP2 phosphorylation by Cdk5 and GSK3β loses its affinity for cytoskeleton proteins, leading to the inhibition of axonal growth. Here, we characterized CRMP2 phosphorylation as the first crucial factor regulating neurotrophic and inhibitory responses after spinal cord injury (SCI). We found that pharmacological inhibition of GSK3β enhanced brain-derived neurotrophic factor (BDNF)-induced axonal growth response in cultured dorsal root ganglion (DRG) neurons. DRG neurons from CRMP2 knock-in (Crmp2KI/KI) mice, where CRMP2 p...Continue Reading

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Citations

Jun 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Marco LeibingerDietmar Fischer
Feb 25, 2020·EMBO Molecular Medicine·Jarred M Griffin, Frank Bradke
Mar 28, 2019·Molecular Neurobiology·Aubin MoutalRajesh Khanna
Jun 16, 2017·Neural Regeneration Research·Jian-Nan Zhang, Jan C Koch
Aug 30, 2018·Scientific Reports·Kye-Im JeonKrystel R Huxlin
May 18, 2019·Biochemical and Biophysical Research Communications·Yuki KinoshitaToshio Ohshima
Mar 2, 2021·Neural Regeneration Research·Shuang ZhuLi-Jun Lin
Apr 29, 2021·Neural Regeneration Research·Zhi-Sheng JiHong-Sheng Lin
Aug 24, 2021·Neural Plasticity·Junko ShibatoSeiji Shioda

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