Schreiber, Rainer and Ousingsawat, Jiraporn and Kunzelmann, Karl (2025) Anoctamin 9 determines Ca2+ signals during activation of T-lymphocytes. FRONTIERS IN IMMUNOLOGY, 16: 1562871. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Background Activation of T-cells is initiated by an increase in intracellular Ca2+, which underlies positive and negative regulation. Because the phospholipid scramblase and ion channel ANO9 (TMEM16J) was shown previously to regulated Ca2+ signals in renal epithelial cells, we asked whether ANO9 demonstrates a similar regulation in T-cells.Methods We used measurements of the intracellular Ca2+ concentration to examine the effects of ANO9 on intracellular Ca2+ signaling and demonstrated expression of ANO9 and its effects on cellular and molecular parameters.Results ANO9 was found to be expressed in human lymphocytes, including the Jurkat T-lymphocyte cell line and mouse lymphocytes. ANO9 has been shown to affect intracellular Ca2+ signals in renal epithelial cells. Here we demonstrate the essential role of ANO9 during initiation of intracellular Ca2+ signals in Jurkat T-cells and isolated mouse lymphocytes. ANO9 is essential for the initial rise in intracellular Ca2+ due to influx of extracellular Ca2+ through store-operated ORAI1 Ca2+ entry channels. ANO9 is indispensable for T-cell function, independent on whether cells are activated by stimulation of the T-cell receptor with CD3-antibody or by PMA/phytohemagglutinin.Conclusions Upon activation of T-cells and formation of the immunological synapse, ANO9 recruits the Ca2+-ATPase (PMCA) to the plasma membrane, which is supported by the scaffolding protein discs large 1 (DLG1). PMCAs maintain low Ca2+ levels near ORAI1 channels thereby suppressing Ca2+-inhibition of ORAI1 and thus retaining store-operated Ca2+ entry (SOCE). It is suggested that ANO9 has a role in interorganelle communication and regulation of cellular protein trafficking, which probably requires its phospholipid scramblase function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMA-MEMBRANE CA2+-ATPASE; CALCIUM MICRODOMAINS; CRAC CHANNELS; PROTEIN; STIM1; MUTATION; FAMILY; STORE; ORAI1; lymphocytes; T-cells; T-cell receptor; TCR; immunological synapse; anoctamin 9; ANO9; 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: | 26 May 2026 05:14 |
| Last Modified: | 26 May 2026 05:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65831 |
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