Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells
TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterol...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4146 |
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| author | Mei Li Jiaojiao Zheng Tian Wu Yulin He Jing Guo Jiao Xu Chuanzhou Gao Shuxian Qu Qianyi Zhang Jiayu Zhao Wei Cheng |
| author_facet | Mei Li Jiaojiao Zheng Tian Wu Yulin He Jing Guo Jiao Xu Chuanzhou Gao Shuxian Qu Qianyi Zhang Jiayu Zhao Wei Cheng |
| author_sort | Mei Li |
| collection | DOAJ |
| description | TRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis. |
| first_indexed | 2024-03-09T10:34:36Z |
| format | Article |
| id | doaj.art-e053e6af135e4aa1834249f57c11df46 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:34:36Z |
| publishDate | 2022-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e053e6af135e4aa1834249f57c11df462023-12-01T21:02:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238414610.3390/ijms23084146Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma CellsMei Li0Jiaojiao Zheng1Tian Wu2Yulin He3Jing Guo4Jiao Xu5Chuanzhou Gao6Shuxian Qu7Qianyi Zhang8Jiayu Zhao9Wei Cheng10Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, ChinaTRPV4 (transient receptor potential vanilloid 4), a calcium permeable TRP ion channel, is known to play a key role in endocytosis. However, whether it contributes to exocytosis remains unclear. Here, we report that activation of TRPV4 induced massive exocytosis in both melanoma A375 cell and heterologous expression systems. We show here that, upon application of TRPV4-specific agonists, prominent vesicle priming from endoplasmic reticulum (ER) was observed, followed by morphological changes of mitochondrial crista may lead to cell ferroptosis. We further identified interactions between TRPV4 and folding/vesicle trafficking proteins, which were triggered by calcium entry through activated TRPV4. This interplay, in turn, enhanced TRPV4-mediated activation of folding and vesicle trafficking proteins to promote exocytosis. Our study revealed a signaling mechanism underlying stimulus-triggered exocytosis in melanoma and highlighted the role of cellular sensor TRPV4 ion channel in mediating ferroptosis.https://www.mdpi.com/1422-0067/23/8/4146TRPV4 ion channelexocytosisA375 cellCa<sup>2+</sup> signalingferroptosis |
| spellingShingle | Mei Li Jiaojiao Zheng Tian Wu Yulin He Jing Guo Jiao Xu Chuanzhou Gao Shuxian Qu Qianyi Zhang Jiayu Zhao Wei Cheng Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells International Journal of Molecular Sciences TRPV4 ion channel exocytosis A375 cell Ca<sup>2+</sup> signaling ferroptosis |
| title | Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells |
| title_full | Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells |
| title_fullStr | Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells |
| title_full_unstemmed | Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells |
| title_short | Activation of TRPV4 Induces Exocytosis and Ferroptosis in Human Melanoma Cells |
| title_sort | activation of trpv4 induces exocytosis and ferroptosis in human melanoma cells |
| topic | TRPV4 ion channel exocytosis A375 cell Ca<sup>2+</sup> signaling ferroptosis |
| url | https://www.mdpi.com/1422-0067/23/8/4146 |
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