Schreiber, Rainer and Ousingsawat, Jiraporn and Kunzelmann, Karl (2020) Targeting of Intracellular TMEM16 Proteins to the Plasma Membrane and Activation by Purinergic Signaling. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (11): 4065. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Anoctamins such as TMEM16A and TMEM16B are Ca2+-dependent Cl- channels activated through purinergic receptor signaling. TMEM16A (ANO1), TMEM16B (ANO2) and TMEM16F (ANO6) are predominantly expressed at the plasma membrane and are therefore well accessible for functional studies. While TMEM16A and TMEM16B form halide-selective ion channels, TMEM16F and probably TMEM16E operate as phospholipid scramblases and nonselective ion channels. Other TMEM16 paralogs are expressed mainly in intracellular compartments and are therefore difficult to study at the functional level. Here, we report that TMEM16E (ANO5), -H (ANO8), -J (ANO9) and K (ANO10) are targeted to the plasma membrane when fused to a C-terminal CAAX (cysteine, two aliphatic amino acids plus methionin, serine, alanin, cystein or glutamin) motif. These paralogs produce Ca2+-dependent ion channels. Surprisingly, expression of the TMEM16 paralogs in the plasma membrane did not produce additional scramblase activity. In contrast, endogenous scrambling induced by stimulation of purinergic P2X7 receptors was attenuated, in parallel with reduced plasma membrane blebbing. This could suggest that intracellular TMEM16 paralogs operate differently when compared to plasma membrane-localized TMEM16F, and may even stabilize intracellular membranes. Alternatively, CAAX tagging, which leads to expression in non-raft compartments of the plasma membrane, may antagonize phosphatidylserine exposure by endogenous raft-located TMEM16F. CAAX-containing constructs may be useful to further investigate the molecular properties of intracellular TMEM16 proteins.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIPID RAFTS; ANO10 MUTATIONS; EXPRESSION; RECEPTOR; PHOSPHATIDYLSERINE; ANOCTAMINS; SECRETION; CHLORIDE; ATAXIA; CYST; ANO5; ANO8; ANO9; ANO10; TMEM16E; TMEM16H; TMEM16J; TMEM16K; scramblase; membrane blebbing; P2X7R; purineric signaling |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 12:41 |
| Last Modified: | 22 Mar 2021 12:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44462 |
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