Schreiber, Rainer and Talbi, Khaoula and Ousingsawat, Jiraporn and Kunzelmann, Karl (2023) A TMEM16J variant leads to dysregulated cytosolic calcium which may lead to renal disease. FASEB JOURNAL, 37 (1): e22683. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
SIGIRR (single immunoglobulin IL-1 related receptor), PKP3 (plakophilin 3), and TMEM16J (anoctamin 9), a putative calcium-activated ion channel and phospholipid scramblase, control the immune response and the extent of inflammation. Variants of SIGIRR/PKP3/TMEM16J lead to severe inflammatory diseases such as pneumonia, enterocolitis, and kidney graft rejection. Meta-analysis of genome-wide association studies identified TMEM16J-T604A as a promotor for chronic kidney disease (CKD), but the disease mechanism and function of TMEM16J remain unknown. Here, we demonstrate TMEM16J as a calcium-activated calcium-permeable channel, which is expressed in the endoplasmic reticulum (ER). TMEM16J controls the intracellular distribution of calcium, and inhibits intracellular receptor-mediated Ca2+ signals and Ca2+-dependent activation of ion channels, but augments transcription and release of pro-inflammatory cytokines. Renal epithelial cells expressing the variant TMEM16J-T604A show enhanced calcium signals when compared to cells expressing wt-TMEM16J, and demonstrate spontaneous transcription and release of cytokines. This study identifies TMEM16J as an important regulator of intracellular Ca2+ signals, ion channel activity, and cytokine release. TMEM16J may therefore affect immune response in renal tissue and immune cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMA-MEMBRANE CA2+-ATPASE; DENDRITIC CELLS; INFLAMMATION; RECEPTOR; SIGIRR; INDICATORS; ANOCTAMINS; IMMUNITY; FAMILY; MEMBER; ANO9; anoctamin 9; Ca2+ signaling; chronic renal failure; renal transplant; TMEM16J |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Mar 2024 15:59 |
| Last Modified: | 07 Mar 2024 15:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58986 |
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