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

Ca influx upon G protein-coupled receptor (GPCR) stimulation is observed as a cytosolic Ca 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), Ca channels on the endoplasmic reticulum, the function of Jaw1 in the Ca dynamics with physiological stimulation remains unclear. In this study, using inducible Jaw1-expressing HEK293 cells, we showed that Jaw1 increases Ca influx by GPCR stimulation via changing the Ca influx oscillation pattern. Furthermore, we showed that Jaw1 increases the Ca release activity of all ITPR subtypes in a subtly different manner. It is well known that the Ca influx oscillation pattern varies from cell type to cell type, therefore these findings provide an insight into the relationship between the heterogeneous Ca dynamics and the specific ITPR and Jaw1 expression patterns.