Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation

Abstract Aquaporins (AQPs) are a family of integral membrane proteins crucial for the flow of water and other small molecules across cellular membranes. The involvement of calmodulin (CaM), a multifunctional calcium-binding protein, has emerged as a central regulator for specific aquaporin homologue...

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Main Authors: Jessica Glas, Johanna Landén, Kristina Hedfalk
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12865-z
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author Jessica Glas
Johanna Landén
Kristina Hedfalk
author_facet Jessica Glas
Johanna Landén
Kristina Hedfalk
author_sort Jessica Glas
collection DOAJ
description Abstract Aquaporins (AQPs) are a family of integral membrane proteins crucial for the flow of water and other small molecules across cellular membranes. The involvement of calmodulin (CaM), a multifunctional calcium-binding protein, has emerged as a central regulator for specific aquaporin homologues from eukaryotes. Using a systematic approach, applying advanced high throughput screening methods in vivo, combining flow cytometry with microscopy, we have evaluated the putative interaction between CaM and the 13 human AQP homologues recombinantly produced in the yeast Saccharomyces cerevisiae. This comprehensive approach is complemented by a theoretical validation of potential CaM binding sites and a review of confirmed CaM binding locations from previous research. Our investigation is based on the established interaction of hAQP0 and CaM and we have successfully validated the binding of hAQP1 and hAQP4 to CaM. Noteworthy, discernibly high fluorescence frequency signals were observed for hAQP8 and hAQP9, which did not correlate with a particularly high production level, supporting protein complex formation with CaM for those AQP homologues. Overall, we present a systematic approach to screen novel membrane protein interactions in vivo, relying on co-expression in yeast of Bimolecular Fluorescence Complementation (BiFC) complexes providing new insights into the regulation of the hAQPs.
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spelling doaj-art-2afea6c8bc504ec187358690d80516922025-08-20T03:42:33ZengNature PortfolioScientific Reports2045-23222025-08-0115111010.1038/s41598-025-12865-zEvaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementationJessica Glas0Johanna Landén1Kristina Hedfalk2Department of Chemistry and Molecular Biology, Gothenburg UniversityDepartment of Chemistry and Molecular Biology, Gothenburg UniversityDepartment of Chemistry and Molecular Biology, Gothenburg UniversityAbstract Aquaporins (AQPs) are a family of integral membrane proteins crucial for the flow of water and other small molecules across cellular membranes. The involvement of calmodulin (CaM), a multifunctional calcium-binding protein, has emerged as a central regulator for specific aquaporin homologues from eukaryotes. Using a systematic approach, applying advanced high throughput screening methods in vivo, combining flow cytometry with microscopy, we have evaluated the putative interaction between CaM and the 13 human AQP homologues recombinantly produced in the yeast Saccharomyces cerevisiae. This comprehensive approach is complemented by a theoretical validation of potential CaM binding sites and a review of confirmed CaM binding locations from previous research. Our investigation is based on the established interaction of hAQP0 and CaM and we have successfully validated the binding of hAQP1 and hAQP4 to CaM. Noteworthy, discernibly high fluorescence frequency signals were observed for hAQP8 and hAQP9, which did not correlate with a particularly high production level, supporting protein complex formation with CaM for those AQP homologues. Overall, we present a systematic approach to screen novel membrane protein interactions in vivo, relying on co-expression in yeast of Bimolecular Fluorescence Complementation (BiFC) complexes providing new insights into the regulation of the hAQPs.https://doi.org/10.1038/s41598-025-12865-zAquaporinCalmodulinSaccharomyces cerevisiaeBimolecular fluorescence complementation
spellingShingle Jessica Glas
Johanna Landén
Kristina Hedfalk
Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
Scientific Reports
Aquaporin
Calmodulin
Saccharomyces cerevisiae
Bimolecular fluorescence complementation
title Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
title_full Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
title_fullStr Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
title_full_unstemmed Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
title_short Evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
title_sort evaluating protein complexes between human aquaporin and calmodulin using biomolecular fluorescence complementation
topic Aquaporin
Calmodulin
Saccharomyces cerevisiae
Bimolecular fluorescence complementation
url https://doi.org/10.1038/s41598-025-12865-z
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AT kristinahedfalk evaluatingproteincomplexesbetweenhumanaquaporinandcalmodulinusingbiomolecularfluorescencecomplementation