Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation
Ca<sup>2+</sup>-dependent gene regulation controls several functions to determine the fate of the cells. Proteins of the nuclear factor of activated T-cells (NFAT) family are Ca<sup>2+</sup> sensitive transcription factors that control the cell growth, proliferation and insul...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8189 |
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| author | Furkan E. Oflaz Zhanat Koshenov Martin Hirtl Rene Rost Olaf A. Bachkoenig Benjamin Gottschalk Corina T. Madreiter-Sokolowski Roland Malli Wolfgang F. Graier |
| author_facet | Furkan E. Oflaz Zhanat Koshenov Martin Hirtl Rene Rost Olaf A. Bachkoenig Benjamin Gottschalk Corina T. Madreiter-Sokolowski Roland Malli Wolfgang F. Graier |
| author_sort | Furkan E. Oflaz |
| collection | DOAJ |
| description | Ca<sup>2+</sup>-dependent gene regulation controls several functions to determine the fate of the cells. Proteins of the nuclear factor of activated T-cells (NFAT) family are Ca<sup>2+</sup> sensitive transcription factors that control the cell growth, proliferation and insulin secretion in β-cells. Translocation of NFAT proteins to the nucleus occurs in a sequence of events that starts with activating calmodulin-dependent phosphatase calcineurin in a Ca<sup>2+</sup>-dependent manner, which dephosphorylates the NFAT proteins and leads to their translocation to the nucleus. Here, we examined the role of IP<sub>3</sub>-generating agonists and near-UV light in the induction of NFATc3 migration to the nucleus in the pancreatic β-cell line INS-1. Our results show that IP<sub>3</sub> generation yields cytosolic Ca<sup>2+</sup> rise and NFATc3 translocation. Moreover, near-UV light exposure generates reactive oxygen species (ROS), resulting in cytosolic Ca<sup>2+</sup> spiking via the L-type Ca<sup>2+</sup> channel and triggers NFATc3 translocation to the nucleus. Using the mitochondria as a Ca<sup>2+</sup> buffering tool, we showed that ROS-induced cytosolic Ca<sup>2+</sup> spiking, not the ROS themselves, was the triggering mechanism of nuclear import of NFATc3. Collectively, this study reveals the mechanism of near-UV light induced NFATc3 migration. |
| first_indexed | 2024-03-10T09:14:30Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:14:30Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea925bb0a9e84673b28c50be2f22236c2023-11-22T05:44:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215818910.3390/ijms22158189Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 TranslocationFurkan E. Oflaz0Zhanat Koshenov1Martin Hirtl2Rene Rost3Olaf A. Bachkoenig4Benjamin Gottschalk5Corina T. Madreiter-Sokolowski6Roland Malli7Wolfgang F. Graier8Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaCa<sup>2+</sup>-dependent gene regulation controls several functions to determine the fate of the cells. Proteins of the nuclear factor of activated T-cells (NFAT) family are Ca<sup>2+</sup> sensitive transcription factors that control the cell growth, proliferation and insulin secretion in β-cells. Translocation of NFAT proteins to the nucleus occurs in a sequence of events that starts with activating calmodulin-dependent phosphatase calcineurin in a Ca<sup>2+</sup>-dependent manner, which dephosphorylates the NFAT proteins and leads to their translocation to the nucleus. Here, we examined the role of IP<sub>3</sub>-generating agonists and near-UV light in the induction of NFATc3 migration to the nucleus in the pancreatic β-cell line INS-1. Our results show that IP<sub>3</sub> generation yields cytosolic Ca<sup>2+</sup> rise and NFATc3 translocation. Moreover, near-UV light exposure generates reactive oxygen species (ROS), resulting in cytosolic Ca<sup>2+</sup> spiking via the L-type Ca<sup>2+</sup> channel and triggers NFATc3 translocation to the nucleus. Using the mitochondria as a Ca<sup>2+</sup> buffering tool, we showed that ROS-induced cytosolic Ca<sup>2+</sup> spiking, not the ROS themselves, was the triggering mechanism of nuclear import of NFATc3. Collectively, this study reveals the mechanism of near-UV light induced NFATc3 migration.https://www.mdpi.com/1422-0067/22/15/8189UV lightROSL-type Ca<sup>2+</sup> channeltranscription factorNFATc3 translocationmitochondrial Ca<sup>2+</sup> buffering |
| spellingShingle | Furkan E. Oflaz Zhanat Koshenov Martin Hirtl Rene Rost Olaf A. Bachkoenig Benjamin Gottschalk Corina T. Madreiter-Sokolowski Roland Malli Wolfgang F. Graier Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation International Journal of Molecular Sciences UV light ROS L-type Ca<sup>2+</sup> channel transcription factor NFATc3 translocation mitochondrial Ca<sup>2+</sup> buffering |
| title | Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation |
| title_full | Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation |
| title_fullStr | Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation |
| title_full_unstemmed | Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation |
| title_short | Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation |
| title_sort | near uv light induced ros production initiates spatial ca sup 2 sup spiking to fire nfatc3 translocation |
| topic | UV light ROS L-type Ca<sup>2+</sup> channel transcription factor NFATc3 translocation mitochondrial Ca<sup>2+</sup> buffering |
| url | https://www.mdpi.com/1422-0067/22/15/8189 |
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