Jaw1/LRMP 可增加 GPCR 刺激后的 Ca2+内流，对每种 ITMP 亚型的活性产生不同的影响。

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

机构信息

Department of Food and Energy Systems Science, Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Tokyo, 184-8588, Japan.

Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, Tokyo, 183-8509, Japan.

出版信息

Sci Rep. 2022 Jun 8;12(1):9476. doi: 10.1038/s41598-022-13620-4.

DOI:10.1038/s41598-022-13620-4

PMID:35676525

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9177832/

Abstract

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.

摘要

钙内流在 G 蛋白偶联受体 (GPCR) 刺激下观察到，作为细胞内钙浓度振荡至关重要，启动下游反应，包括细胞增殖、分化和细胞间通讯。虽然已经知道 Jaw1 与肌醇 1,4,5-三磷酸受体 (ITPRs)，内质网上的钙通道相互作用，但 Jaw1 在生理刺激下的钙动力学功能仍不清楚。在这项研究中，我们使用可诱导表达 Jaw1 的 HEK293 细胞表明，Jaw1 通过改变钙内流振荡模式来增加 GPCR 刺激下的钙内流。此外，我们表明 Jaw1 以略有不同的方式增加所有 ITPR 亚型的钙释放活性。众所周知，钙内流振荡模式因细胞类型而异，因此这些发现为了解异质钙动力学与特定的 ITPR 和 Jaw1 表达模式之间的关系提供了一个视角。