Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and @entity158 -processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional @entity4176 receptors (KARs), one of three sub-families of ionotropic @entity3264 receptors, as well as the putative @entity69428 auxiliary subunit @entity69429 . @entity69429 markedly alters recombinant @entity69428 function but has yet to be confirmed as an auxiliary subunit that assembles with and alters function of endogenous KARs. KARs in neonatal DRG require the @entity10092 subunit as a necessary constituent, but it is unclear to what extent other @entity69428 subunits contribute to the function and the proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of @entity3264 release at the DRG-dorsal horn synapse. Additionally, KARs containing the @entity10092 subunit are implicated in modes of persistent but not acute @entity158 signaling. We show here that @entity69429 protein is highly expressed in neonatal DRG and modifies @entity69428 gating in DRG neurons in a developmentally-regulated fashion in @entity19 . While normally at very low levels in adult DRG neurons, @entity69429 protein expression can be upregulated via MEK/ERK signaling and following sciatic nerve crush, and @entity69429 (-/-) neurons from adult @entity19 have stunted neurite outgrowth. These data confirm that @entity69429 is a bona fide @entity69428 auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that @entity69429 assembly is critical to @entity69428 modulation of DRG neuron process outgrowth.SIGNIFICANCE STATEMENTPain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express @entity4176 receptors (KARs), a sub-family of @entity3264 receptors, which modulate neurite outgrowth and regulate @entity3264 release at the DRG to dorsal horn synapse. The putative @entity69428 auxiliary subunit @entity69429 is also expressed in DRG. We show here that it is a developmentally down-regulated but dynamic component of KARs in these neurons, that it contributes to regulated neurite regrowth in adult neurons, and that it is increased in adult @entity19 following @entity128 . Our data confirm @entity69429 as a @entity69428 auxiliary subunit and expand our knowledge of the molecular composition of KARs in nociceptive neurons, a key piece in understanding the mechanistic contribution of @entity69428 signaling to @entity158 processing circuits.

XXXX assembles with @entity4176 receptors in DRG neurons during development and modulates neurite outgrowth in adult sensory neurons.

@entity3264 :: ('D018698', 'Chemical') :: ['glutamate'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity69429 :: ('74513(Tax:10090)', 'Gene') :: ['Neto2'] @entity128 :: ('MESH:D020209', 'Disease') :: ['nerve injury'] @entity10092 :: ('14805(Tax:10090)', 'Gene') :: ['GluK1'] @entity4176 :: ('MESH:D007608', 'Chemical') :: ['kainate'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain'] @entity69428 :: ('56348(Tax:10090)', 'Gene') :: ['KAR']
@entity69429 :: (74513(Tax:10090),Gene) :: ['Neto2']
