PT  - JOURNAL ARTICLE
AU  - Alexandra Hogea
AU  - Shihab Shah
AU  - Frederick Jones
AU  - Chase M Carver
AU  - Han Hao
AU  - Ce Liang
AU  - Dongyang Huang
AU  - Xiaona Du
AU  - Nikita Gamper
TI  - Junctophilin-4 is essential for signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons
AID  - 10.1101/842476
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 842476
4099  - http://biorxiv.org/content/early/2019/11/15/842476.short
4100  - http://biorxiv.org/content/early/2019/11/15/842476.full
AB  - Junctions of endoplasmic reticulum and plasma membrane (ER-PM junctions) serve as signaling hubs in prokaryotic cells. ER-PM junctions are present in peripheral sensory neurons and are necessary for pro-inflammatory G protein coupled receptor signalling and for inflammatory pain generation. Yet, the principles of ER-PM junctions assembly and maintenance, as well as their role in inflammatory signaling in sensory neurons are only beginning to emerge. Here we discovered that a member of the junctophilin family of proteins, JPH4, is abundantly expressed in rat dorsal root ganglion (DRG) neurons and is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the ER-PM junctions in response to the G-protein induced ER Ca2+ store depletion. Furthermore, we demonstrate a key role of the JPH4 and ER Ca2+ stores in the maintenance of inflammatory pain. Indeed, knockdown of JPH4 expression in DRG in vivo significantly reduced the duration of pain produced by inflammatory mediator bradykinin. Since the ER supplies Ca2+ for the excitatory action of multiple inflammatory mediators, we suggest that junctional Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms.