IRAG2 Interacts with IP<sub>3</sub>-Receptor Types 1, 2, and 3 and Regulates Intracellular Ca<sup>2+</sup> in Murine Pancreatic Acinar Cells
The inositol 1,4,5-triphosphate receptor-associated 2 (IRAG2) is also known as Jaw1 or lymphoid-restricted membrane protein (LRMP) and shares homology with the inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate 1 (IRAG1). IRAG1 interacts with inositol trisphosphate receptors (IP&l...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/24/13409 |
| Summary: | The inositol 1,4,5-triphosphate receptor-associated 2 (IRAG2) is also known as Jaw1 or lymphoid-restricted membrane protein (LRMP) and shares homology with the inositol 1,4,5-triphosphate receptor-associated cGMP kinase substrate 1 (IRAG1). IRAG1 interacts with inositol trisphosphate receptors (IP<sub>3</sub> receptors /IP<sub>3</sub>R) via its coiled-coil domain and modulates Ca<sup>2+</sup> release from intracellular stores. Due to the homology of IRAG1 and IRAG2, especially in its coiled-coil domain, it is possible that IRAG2 has similar interaction partners like IRAG1 and that IRAG2 also modulates intracellular Ca<sup>2+</sup> signaling. In our study, we localized IRAG2 in pancreatic acinar cells of the exocrine pancreas, and we investigated the interaction of IRAG2 with IP<sub>3</sub> receptors and its impact on intracellular Ca<sup>2+</sup> signaling and exocrine pancreatic function, like amylase secretion. We detected the interaction of IRAG2 with different subtypes of IP<sub>3</sub>R and altered Ca<sup>2+</sup> release in pancreatic acinar cells from mice lacking IRAG2. IRAG2 deficiency decreased basal levels of intracellular Ca<sup>2+</sup>, suggesting that IRAG2 leads to activation of IP<sub>3</sub>R under unstimulated basal conditions. Moreover, we observed that loss of IRAG2 impacts the secretion of amylase. Our data, therefore, suggest that IRAG2 modulates intracellular Ca<sup>2+</sup> signaling, which regulates exocrine pancreatic function. |
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| ISSN: | 1661-6596 1422-0067 |