Research ArticlePain

Ubiquitination and functional modification of GluN2B subunit–containing NMDA receptors by Cbl-b in the spinal cord dorsal horn

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Science Signaling  30 Jun 2020:
Vol. 13, Issue 638, eaaw1519
DOI: 10.1126/scisignal.aaw1519

A painful return to developmental NMDAR activity

Neuronal sensitivity is mediated, in part, by NMDA receptor (NMDAR) signaling, and increased abundance of GluN2B-containing NMDARs in sensory neuronal synapses is associated with enhanced nociception and pain. Using rodents, Zhang et al. found that GluN2B content in the sensory neurons of the spine is progressively restricted during early development and maintained at low abundance by the E3 ubiquitin ligase Cbl-b during adulthood. However, peripheral inflammation induced the dephosphorylation of Cbl-b and impaired its interaction with GluN2B, and the increase in GluN2B abundance enhanced NMDAR activity and neuronal sensitivity to touch. Identifying a way to target this mechanism might be therapeutic in patients suffering from inflammatory peripheral neuropathy.

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