Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart
Store-operated Ca2+ entry (SOCE) is an essential Ca2+ signaling mechanism present in most animal cells. SOCE refers to Ca2+ influx that is activated by depletion of sarco/endoplasmic reticulum (S/ER) Ca2+ stores. The main components of SOCE are STIM and Orai. STIM proteins function as S/ER Ca2+ sens...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2020-03-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/9/3/bio049999 |
| _version_ | 1818859665833852928 |
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| author | Courtney E. Petersen Matthew J. Wolf Jeremy T. Smyth |
| author_facet | Courtney E. Petersen Matthew J. Wolf Jeremy T. Smyth |
| author_sort | Courtney E. Petersen |
| collection | DOAJ |
| description | Store-operated Ca2+ entry (SOCE) is an essential Ca2+ signaling mechanism present in most animal cells. SOCE refers to Ca2+ influx that is activated by depletion of sarco/endoplasmic reticulum (S/ER) Ca2+ stores. The main components of SOCE are STIM and Orai. STIM proteins function as S/ER Ca2+ sensors, and upon S/ER Ca2+ depletion STIM rearranges to S/ER-plasma membrane junctions and activates Orai Ca2+ influx channels. Studies have implicated SOCE in cardiac hypertrophy pathogenesis, but SOCE's role in normal heart physiology remains poorly understood. We therefore analyzed heart-specific SOCE function in Drosophila, a powerful animal model of cardiac physiology. We show that heart-specific suppression of Stim and Orai in larvae and adults resulted in reduced contractility consistent with dilated cardiomyopathy. Myofibers were also highly disorganized in Stim and Orai RNAi hearts, reflecting possible decompensation or upregulated stress signaling. Furthermore, we show that reduced heart function due to SOCE suppression adversely affected animal viability, as heart specific Stim and Orai RNAi animals exhibited significant delays in post-embryonic development and adults died earlier than controls. Collectively, our results demonstrate that SOCE is essential for physiological heart function, and establish Drosophila as an important model for understanding the role of SOCE in cardiac pathophysiology. |
| first_indexed | 2024-12-19T09:15:48Z |
| format | Article |
| id | doaj.art-2e4c23acc93e4660b28f6205e923ac9b |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:15:48Z |
| publishDate | 2020-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-2e4c23acc93e4660b28f6205e923ac9b2022-12-21T20:28:05ZengThe Company of BiologistsBiology Open2046-63902020-03-019310.1242/bio.049999049999Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heartCourtney E. Petersen0Matthew J. Wolf1Jeremy T. Smyth2 Graduate Program in Molecular and Cellular Biology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA Division of Cardiovascular Medicine, Department of Medicine, The University of Virginia School of Medicine, Charlottesville, VA 22908, USA Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814, USA Store-operated Ca2+ entry (SOCE) is an essential Ca2+ signaling mechanism present in most animal cells. SOCE refers to Ca2+ influx that is activated by depletion of sarco/endoplasmic reticulum (S/ER) Ca2+ stores. The main components of SOCE are STIM and Orai. STIM proteins function as S/ER Ca2+ sensors, and upon S/ER Ca2+ depletion STIM rearranges to S/ER-plasma membrane junctions and activates Orai Ca2+ influx channels. Studies have implicated SOCE in cardiac hypertrophy pathogenesis, but SOCE's role in normal heart physiology remains poorly understood. We therefore analyzed heart-specific SOCE function in Drosophila, a powerful animal model of cardiac physiology. We show that heart-specific suppression of Stim and Orai in larvae and adults resulted in reduced contractility consistent with dilated cardiomyopathy. Myofibers were also highly disorganized in Stim and Orai RNAi hearts, reflecting possible decompensation or upregulated stress signaling. Furthermore, we show that reduced heart function due to SOCE suppression adversely affected animal viability, as heart specific Stim and Orai RNAi animals exhibited significant delays in post-embryonic development and adults died earlier than controls. Collectively, our results demonstrate that SOCE is essential for physiological heart function, and establish Drosophila as an important model for understanding the role of SOCE in cardiac pathophysiology.http://bio.biologists.org/content/9/3/bio049999cardiomyopathycardiacstore-operated calcium entrystimoraidrosophila |
| spellingShingle | Courtney E. Petersen Matthew J. Wolf Jeremy T. Smyth Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart Biology Open cardiomyopathy cardiac store-operated calcium entry stim orai drosophila |
| title | Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart |
| title_full | Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart |
| title_fullStr | Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart |
| title_full_unstemmed | Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart |
| title_short | Suppression of store-operated calcium entry causes dilated cardiomyopathy of the Drosophila heart |
| title_sort | suppression of store operated calcium entry causes dilated cardiomyopathy of the drosophila heart |
| topic | cardiomyopathy cardiac store-operated calcium entry stim orai drosophila |
| url | http://bio.biologists.org/content/9/3/bio049999 |
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