Phosphorylated CRMP2 Regulates Spinal Nociceptive Neurotransmission

Molecular Neurobiology
Jie YuR Khanna

Abstract

The collapsin response mediator protein 2 (CRMP2) has emerged as a central node in assembling nociceptive signaling complexes involving voltage-gated ion channels. Concerted actions of post-translational modifications, phosphorylation and SUMOylation, of CRMP2 contribute to regulation of pathological pain states. In the present study, we demonstrate a novel role for CRMP2 in spinal nociceptive transmission. We found that, of six possible post-translational modifications, three phosphorylation sites on CRMP2 were critical for regulating calcium influx in dorsal root ganglion sensory neurons. Of these, only CRMP2 phosphorylated at serine 522 by cyclin-dependent kinase 5 (Cdk5) contributed to spinal neurotransmission in a bidirectional manner. Accordingly, expression of a non-phosphorylatable CRMP2 (S522A) decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), whereas expression of a constitutively phosphorylated CRMP2 (S522D) increased the frequency of sEPSCs. The presynaptic nature of CRMP2's actions was further confirmed by pharmacological antagonism of Cdk5-mediated CRMP2 phosphorylation with S-N-benzy-2-acetamido-3-methoxypropionamide ((S)-lacosamide; (S)-LCM) which (i) decreased sEPSC frequency, (i...Continue Reading

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Citations

Dec 7, 2019·Journal of Molecular Neuroscience : MN·Zhongqi ZhangGuoqing Guo
Aug 11, 2020·Pain·Kimberly GomezRajesh Khanna
Mar 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xu ChenYitao Qi

Methods Mentioned

BETA
dissection
Transfection
protein assay
transfections
enzyme-linked immunosorbent assay

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