Research ArticlePain

Palmitoylation of δ-catenin promotes kinesin-mediated membrane trafficking of Nav1.6 in sensory neurons to promote neuropathic pain

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Science Signaling  27 Mar 2018:
Vol. 11, Issue 523, eaar4394
DOI: 10.1126/scisignal.aar4394

Palmitoylation and pain

Chronic pain is associated with inflammation and increased synaptic activity in sensory neurons. Zhang et al. found that induction of the inflammatory cytokine TNF-α after chemotherapy or nerve injury in rats promoted the formation of a complex between the cell adhesion protein δ-catenin, the voltage-gated sodium channel Nav1.6, and the kinesin motor protein KIF3A, which increased the trafficking of the sodium channel to the cell membrane. Formation of this complex was dependent on the palmitoylation of δ-catenin, and inhibiting the activity of palmitoyl acyltransferases prevented the increase in both Nav1.6 surface abundance in sensory neurons and pain sensitivity in rats. These findings reveal potential therapeutic targets for treating chronic, neuropathic pain in patients.

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