Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes
Abstract A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding. The prominent member ADAM10 has been linked to several pathologies such as Alzheimer’s disease, bacterial infection, cancer development and...
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BMC
2024-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01891-5 |
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| author | Federico Guillermo Gharzia Ahmad Aljohmani Andreas Beck Stephan E. Philipp Daniela Yildiz |
| author_facet | Federico Guillermo Gharzia Ahmad Aljohmani Andreas Beck Stephan E. Philipp Daniela Yildiz |
| author_sort | Federico Guillermo Gharzia |
| collection | DOAJ |
| description | Abstract A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding. The prominent member ADAM10 has been linked to several pathologies such as Alzheimer’s disease, bacterial infection, cancer development and metastasis. Although the regulation of the ADAM10 activity by calcium influx and calmodulin inhibition has been reported, the spatiotemporal regulation of Ca2+-dependent ADAM10 activation and the required source of Ca2+ ions have not been thoroughly studied. In the present study, we observed the rapid Ca2+-dependent activation of ADAM10 in A549 lung carcinoma cells upon stimulation with ionomycin. The calmodulin-inhibitors trifluoperazine and ophiobolin A mediated delayed activation of ADAM10, which apparently did not depend on intracellular Ca2+ in the case of trifluoperazine. Furthermore, the surface translocation and release of ADAM10 in extracellular vesicles exhibited different kinetics and were only partially linked to catalytic activation. Finally, ADAM10 activation was observed after the entry of Ca2+ through certain channels, such as canonical members of transient receptor potential (TRP) channels. Therefore, the opening of particular channels for Ca2+ entry points and subsequent Ca2+ flux as well as the temporal aspects of the consequent increase in Ca2+ levels, must be considered for future therapeutic options involving the increasing or decreasing ADAM10 activity. |
| format | Article |
| id | doaj-art-d282e46f7a9e46299ba8fa758cf97e7f |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-d282e46f7a9e46299ba8fa758cf97e7f2024-11-10T12:35:04ZengBMCCell Communication and Signaling1478-811X2024-11-0122111810.1186/s12964-024-01891-5Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changesFederico Guillermo Gharzia0Ahmad Aljohmani1Andreas Beck2Stephan E. Philipp3Daniela Yildiz4Molecular Pharmacology, PZMS, Saarland UniversityMolecular Pharmacology, PZMS, Saarland UniversityInstitute of Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland UniversityInstitute of Experimental and Clinical Pharmacology and Toxicology, PZMS, Saarland UniversityMolecular Pharmacology, PZMS, Saarland UniversityAbstract A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding. The prominent member ADAM10 has been linked to several pathologies such as Alzheimer’s disease, bacterial infection, cancer development and metastasis. Although the regulation of the ADAM10 activity by calcium influx and calmodulin inhibition has been reported, the spatiotemporal regulation of Ca2+-dependent ADAM10 activation and the required source of Ca2+ ions have not been thoroughly studied. In the present study, we observed the rapid Ca2+-dependent activation of ADAM10 in A549 lung carcinoma cells upon stimulation with ionomycin. The calmodulin-inhibitors trifluoperazine and ophiobolin A mediated delayed activation of ADAM10, which apparently did not depend on intracellular Ca2+ in the case of trifluoperazine. Furthermore, the surface translocation and release of ADAM10 in extracellular vesicles exhibited different kinetics and were only partially linked to catalytic activation. Finally, ADAM10 activation was observed after the entry of Ca2+ through certain channels, such as canonical members of transient receptor potential (TRP) channels. Therefore, the opening of particular channels for Ca2+ entry points and subsequent Ca2+ flux as well as the temporal aspects of the consequent increase in Ca2+ levels, must be considered for future therapeutic options involving the increasing or decreasing ADAM10 activity.https://doi.org/10.1186/s12964-024-01891-5CalciumProteolysisMetalloproteinasesExosomesTransient receptor potential channelsJunction and adhesion molecules |
| spellingShingle | Federico Guillermo Gharzia Ahmad Aljohmani Andreas Beck Stephan E. Philipp Daniela Yildiz Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes Cell Communication and Signaling Calcium Proteolysis Metalloproteinases Exosomes Transient receptor potential channels Junction and adhesion molecules |
| title | Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes |
| title_full | Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes |
| title_fullStr | Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes |
| title_full_unstemmed | Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes |
| title_short | Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes |
| title_sort | regulation of adam10 activity through microdomain dependent intracellular calcium changes |
| topic | Calcium Proteolysis Metalloproteinases Exosomes Transient receptor potential channels Junction and adhesion molecules |
| url | https://doi.org/10.1186/s12964-024-01891-5 |
| work_keys_str_mv | AT federicoguillermogharzia regulationofadam10activitythroughmicrodomaindependentintracellularcalciumchanges AT ahmadaljohmani regulationofadam10activitythroughmicrodomaindependentintracellularcalciumchanges AT andreasbeck regulationofadam10activitythroughmicrodomaindependentintracellularcalciumchanges AT stephanephilipp regulationofadam10activitythroughmicrodomaindependentintracellularcalciumchanges AT danielayildiz regulationofadam10activitythroughmicrodomaindependentintracellularcalciumchanges |