Junctophilin?4 facilitates inflammatory signalling at plasma membrane?endoplasmic reticulum junctions in sensory neurons

Key points Rat somatosensory neurons express a junctional protein, junctophilin-4 (JPH4) JPH4 is necessary for the formation of store operated Ca2+ entry (SOCE) complex at junctions between plasma membrane and endoplasmic reticulum in these neurons. Knockdown impairs refill signalling sensory In vivo knockdown dorsal root ganglion (DRG) significantly attenuated experimentally induced inflammatory pain rats. Junctional nanodomain maintained by an important contributor to mechanisms. Abstract Junctions (ER-PM junctions) form nanodomains eukaryotic cells. ER-PM are present peripheral fidelity G protein coupled receptor (GPCR) signalling. Yet little known about assembly, maintenance physiological role transduction. Using fluorescence imaging, proximity ligation, super-resolution microscopy, vitro gene we demonstrate that member junctophilin family, (JPH4), rat Thus show localises areas co-clusters with SOCE proteins STIM1 Orai1 upon ER depletion. Furthermore, key pain-like response mediator bradykinin. Indeed, shortened duration nocifensive behaviour hindpaw injection bradykinin Since supplies excitatory action multiple mediators, suggest