Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Nav1.6 in sensory neurons to promote neuropathic pain
2018
Palmitoylation of δ-catenin is critical to synapse plasticity and memory formation. We found that δ-catenin palmitoylation is also instrumental in the development of neuropathic pain. The abundances of palmitoylated δ-catenin and the palmitoyl acyltransferase DHHC3 were increased in dorsal root ganglion (DRG) sensory neurons in rat models of neuropathic pain. Inhibiting palmitoyl acyltransferases or decreasing δ-catenin abundance in the DRG by intrathecal injection of 2-bromopalmitate or shRNA, respectively, alleviated oxaliplatin or nerve injury–induced neuropathic pain in the rats. The palmitoylation of δ-catenin, which was induced by the inflammatory cytokine TNF-α, facilitated its interaction with the voltage-gated sodium channel Na v 1.6 and the kinesin motor protein KIF3A, which promoted the trafficking of Na v 1.6 to the plasma membrane in DRG neurons and contributed to mechanical hypersensitivity and allodynia in rats. These findings suggest that a palmitoylation-mediated KIF3A/δ-catenin/Na v 1.6 complex enhances the transmission of mechanical and nociceptive signals; thus, blocking this mechanism may be therapeutic in patients with neuropathic pain.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
48
References
20
Citations
NaN
KQI