Jaw1/LRMP increases Ca2+ influx upon GPCR stimulation with heterogeneous effect on the activity of each ITPR subtype

Abstract

AbstractCa2+influx upon G protein-coupled receptor (GPCR) stimulation is observed as a cytosolic Ca2+concentration oscillation crucial to initiating downstream responses including cell proliferation, differentiation, and cell–cell communication. Although Jaw1 is known to interact with inositol 1,4,5-triphosphate receptor (ITPRs), Ca2+channels on the endoplasmic reticulum, the function of Jaw1 in the Ca2+dynamics with physiological stimulation remains unclear. In this study, using inducible Jaw1-expressing HEK293 cells, we showed that Jaw1 increases Ca2+influx by GPCR stimulation via changing the Ca2+influx oscillation pattern. Furthermore, we showed that Jaw1 increases the Ca2+release activity of all ITPR subtypes in a subtly different manner. It is well known that the Ca2+influx oscillation pattern varies from cell type to cell type, therefore these findings provide an insight into the relationship between the heterogeneous Ca2+dynamics and the specific ITPR and Jaw1 expression patterns.