The CaMKII/MLC1 Axis Confers Ca2+-Dependence to Volume-Regulated Anion Channels (VRAC) in Astrocytes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Cultures and Treatments
2.2. Generation of U251 Cell Lines Expressing MLC1-T17A and T17D Mutants
2.3. Immunofluorescence Staining (IF)
2.4. Pull-Down Assay and Immunoprecipitation
2.5. Protein Extract Preparation and Western Blotting (WB)
2.6. In Vitro Kinase Assay for CaMKII
2.7. Mass Spectrometry Analysis
2.8. Electrophysiology
2.9. Fura-2-Based Ca2+ Imaging
2.10. Statistical Analysis
3. Results
3.1. Ca2+-Dependent Protein Kinases II (CaMKII) Binds MLC1 Protein in Astrocytes
3.2. CaMKII Phosphorylates MLC1 Protein at the Amino Acid Residue Threonine 17
3.3. CaMKII-Mediated Phosphorylation of MLC1 in Response to Intracellular Ca2+ Increase Affects MLC1 Protein Assembly and Stability in U251 Cells
3.4. MLC1 Potentiates VRAC-Mediated ICl,swell in U251 Cells
3.5. MLC1 Potentiates VRAC-Mediated ICl,swelll in U251 Cells through a CaMKII-Dependent Mechanism
3.6. Hyposmotic Challenge Induces Ca2+ Influx and Ca2+ Release in U251 Cells
3.7. CaMKII/MLC1-Dependent Enhancement of ICl,swell Requires Release of Ca2+ from Intracellular Stores Induced by Extracellular Ca2+ Influx
4. Discussion
4.1. CamKII Binds and Phosphorylates MLC1
4.2. CaMKII-Mediated Phosphorylation of MLC1 Confers Ca2+-Dependence to VRAC Activation
4.3. Significance of Astrocyte Ca2+ Signaling in MLC Pathogenesis and Beyond
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Brignone, M.S.; Lanciotti, A.; Michelucci, A.; Mallozzi, C.; Camerini, S.; Catacuzzeno, L.; Sforna, L.; Caramia, M.; D’Adamo, M.C.; Ceccarini, M.; et al. The CaMKII/MLC1 Axis Confers Ca2+-Dependence to Volume-Regulated Anion Channels (VRAC) in Astrocytes. Cells 2022, 11, 2656. https://doi.org/10.3390/cells11172656
Brignone MS, Lanciotti A, Michelucci A, Mallozzi C, Camerini S, Catacuzzeno L, Sforna L, Caramia M, D’Adamo MC, Ceccarini M, et al. The CaMKII/MLC1 Axis Confers Ca2+-Dependence to Volume-Regulated Anion Channels (VRAC) in Astrocytes. Cells. 2022; 11(17):2656. https://doi.org/10.3390/cells11172656
Chicago/Turabian StyleBrignone, Maria Stefania, Angela Lanciotti, Antonio Michelucci, Cinzia Mallozzi, Serena Camerini, Luigi Catacuzzeno, Luigi Sforna, Martino Caramia, Maria Cristina D’Adamo, Marina Ceccarini, and et al. 2022. "The CaMKII/MLC1 Axis Confers Ca2+-Dependence to Volume-Regulated Anion Channels (VRAC) in Astrocytes" Cells 11, no. 17: 2656. https://doi.org/10.3390/cells11172656