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Junctophilin-4 facilitates inflammatory signaling at plasma membrane-endoplasmic reticulum junctions in sensory neurons.
Abstract
Rat somatosensory neurons express junctional protein, junctophilin-4 (JPH4) JPH4 is necessary for the formation of store operated Ca entry (SOCE) complex at the junctions between plasma membrane and endoplasmic reticulum in these neurons. Knockdown of JPH4 impairs endoplasmic reticulum Ca store refill and junctional Ca signalling in sensory neurons. In vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly attenuated experimentally-induced inflammatory pain in rats. Junctional nanodomain Ca signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms.