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

Jaw1/LRMP在GPCR刺激后增加Ca2+内流,但对每种ITPR亚型的活性具有异质性影响。

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作者:Wataru Okumura,Takuma Kozono,Hiroyuki Sato,Hitomi Matsui,Tsubasa Takagi,Takashi Tonozuka,Atsushi Nishikawa

Abstract

Ca2+ 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.

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