Cell specific regulation of NaV1.7 activity and trafficking in rat nodose ganglia neurons

Santiago I. Loya-López, Paz Duran, Dongzhi Ran, Aida Calderon-Rivera, Kimberly Gomez, Aubin Moutal, Rajesh Khanna

Research output: Contribution to journalArticlepeer-review


The voltage-gated sodium NaV1.7 channel sets the threshold for electrogenesis. Mutations in the gene encoding human NaV1.7 (SCN9A) cause painful neuropathies or pain insensitivity. In dorsal root ganglion (DRG) neurons, activity and trafficking of NaV1.7 are regulated by the auxiliary collapsin response mediator protein 2 (CRMP2). Specifically, preventing addition of a small ubiquitin-like modifier (SUMO), by the E2 SUMO-conjugating enzyme Ubc9, at lysine-374 (K374) of CRMP2 reduces NaV1.7 channel trafficking and activity. We previously identified a small molecule, designated 194, that prevented CRMP2 SUMOylation by Ubc9 to reduce NaV1.7 surface expression and currents, leading to a reduction in spinal nociceptive transmission, and culminating in normalization of mechanical allodynia in models of neuropathic pain. In this study, we investigated whether NaV1.7 control via CRMP2-SUMOylation is conserved in nodose ganglion (NG) neurons. This study was motivated by our desire to develop 194 as a safe, non-opioid substitute for persistent pain, which led us to wonder how 194 would impact NaV1.7 in NG neurons, which are responsible for driving the cough reflex. We found functioning NaV1.7 channels in NG neurons; however, they were resistant to downregulation via either CRMP2 knockdown or pharmacological inhibition of CRMP2 SUMOylation by 194. CRMP2 SUMOylation and interaction with NaV1.7 was consered in NG neurons but the endocytic machinery was deficient in the endocytic adaptor protein Numb. Overexpression of Numb rescued CRMP2-dependent regulation on NaV1.7, rendering NG neurons sensitive to 194. Altogether, these data point at the existence of cell-specific mechanisms regulating NaV1.7 trafficking.

Original languageEnglish (US)
Article number100109
JournalNeurobiology of Pain
StatePublished - Aug 1 2022


  • CRMP2
  • NaV1.7
  • Nodose ganglia neurons
  • Numb
  • Trafficking

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


Dive into the research topics of 'Cell specific regulation of NaV1.7 activity and trafficking in rat nodose ganglia neurons'. Together they form a unique fingerprint.

Cite this