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Multispectral Imaging and Single-Cell Analysis with Genetically Encoded Biosensors Unveil Complex Interactions between Extracellular ATP and Intracellular Calcium Skip to content Yıl 2024, Cilt: 45 Sayı: 2, 360 – 365, 30.06.2024
Emrah Eroğlu
https://doi.org/10.17776/csj.1462654
Öz The dynamic interplay between extracellular ATP (eATP) and intracellular calcium ([Ca2+]i) serves as a pivotal signaling axis in cellular physiology, influencing a myriad of cellular processes. Traditionally recognized as an energy currency within the cell, ATP has emerged as a multifunctional signaling molecule that orchestrates diverse cellular responses through activation of purinergic receptors. The complex link between ATP signaling and calcium dynamics plays a central role in cellular communication and homeostasis. Advancements in imaging technologies such as development of genetically encoded biosensors have revolutionized the study of cellular signaling dynamics, enabling visualization of the spatiotemporal aspects of eATP and [Ca2+]i in real-time. The convergence of eATP signaling and [Ca2+]i dynamics serves as a central hub in cellular communication. In this study, utilizing bicistronic construct biosensors for multispectral imaging of [Ca2+]i responses to eATP, we show that distinct concentrations of eATP administration reveal complex intracellular [Ca2+]i responses, potentially attributed to receptor desensitization. Single-cell co-imaging uncovers [Ca2+]i heterogeneity, emphasizing the significance of individual cell dynamics in eATP-induced calcium signaling. Therefore, this study sheds light on the intricacies of eATP-induced calcium signaling, providing insights valuable for basic research and therapeutic applications.
Anahtar Kelimeler Calcium signaling, ATP signaling, Single cell imaging, Genetically encoded eiosensors, Multispectral imaging
Etik Beyan N.A.
Proje Numarası EMBO IG-5322-2023
Teşekkür This research was supported by funds from the European Molecular Biology Organization EMBO (IG-5322-2023. The author acknowledges Asal Ghaffari Zaki for English language proofreading. Figure 1A was generated with Biorender (Licence code: ME26EKR3WY).
Kaynakça [1] Arcuino G, Lin JHC, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M. Intercellular calcium signaling mediated by point-source burst release of ATP, Proc. Natl. Acad. Sci., 99 (15) (2002) 9840–9845. [2] Cisneros-Mejorado A, Pérez-Samartín A, Gottlieb M, Matute C. ATP signaling in brain: release, excitotoxicity and potential therapeutic targets, Cell. Mol. Neurobiol., 35 (1) (2015) 1–6. [3] Depaoli MR, Karsten F, Madreiter-Sokolowski CT, Klec C, Gottschalk B, Bischof H, Eroglu E, Waldeck-Weiermair M, Simmen T, Graier WF, Malli R. Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells, Cell Rep., 25 (2) (2018) 501-512. [4] Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F, Wieckowski MR, Pinton P., ATP synthesis and storage, Purinergic Signal., 8 (3) (2012) 343–357. [5] Eersapah V, Hugel S, Schlichter R., High-resolution detection of ATP release from single cultured mouse dorsal horn spinal cord glial cells and its modulation by noradrenaline, Purinergic Signal., 15 (3) (2019) 403–420. [6] Fields RD, Burnstock G., Purinergic signalling in neuron-glia interactions, Nat. Rev. Neurosci., 7 (6) (2006) 423–436. [7] Eroglu E, Saravi SSS, Sorrentino A, Steinhorn B, Michel T., Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods, Proc. Natl. Acad. Sci. U. S. A., 116 (40) (2019) 20210–20217. [8] Eroglu E, Hallström S, Bischof H, Opelt M, Schmidt K, Mayer B, Waldeck-Weiermair M, Graier WF, Malli R., Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells, Nitric Oxide Biol. Chem., 70 (2017) 59–67. [9] Barry VA, Cheek TR., Extracellular ATP triggers two functionally distinct calcium signalling pathways in PC12 cells, J. Cell Sci., 107 ( Pt 2) (1994) 451–462. [10] Burnstock G., Purine and purinergic receptors, Brain Neurosci. Adv., 2 (2018) 2398212818817494. [11] Molcak H, Jiang K, Campbell CJ, Matsubara JA., Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration, Front. Neurosci., 17 (2023) 1216489. [12] Eroglu E, Gottschalk B, Charoensin S, Blass S, Bischof H, Rost R, Madreiter-Sokolowski CT, Pelzmann B, Bernhart E, Sattler W, Hallström S, Malinski T, Waldeck-Weiermair M, Graier WF, Malli R., Development of novel FP-based probes for live-cell imaging of nitric oxide dynamics, Nat. Commun., 7 (1) (2016). [13] Eroglu E, Rost R, Bischof H, Blass S, Schreilechner A, Gottschalk B, Depaoli MR, Klec C, Charoensin S, Madreiter-Sokolowski CT, Ramadani J, Waldeck-Weiermair M, Graier WF, Malli R., Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells, J. Vis. Exp. JoVE, (121) (2017) 55486. [14] Eroglu E, Charoensin S, Bischof H, Ramadani J, Gottschalk B, Depaoli MR, Waldeck-Weiermair M, Graier WF, Malli R., Genetic biosensors for imaging nitric oxide in single cells, Free Radic. Biol. Med., 128 (2018) 50–58. [15] Wu Z, He K, Chen Y, Li H, Pan S, Li B, Liu T, Xi F, Deng F, Wang H, Du J, Jing M, Li Y., A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo, Neuron, 110 (5) (2022) 770-782. [16] Conley JM, Radhakrishnan S, Valentino SA, Tantama M., Imaging extracellular ATP with a genetically-encoded, ratiometric fluorescent sensor, PLoS ONE, 12 (11) (2017) e0187481. [17] Lobas MA, Tao R, Nagai J, Kronschläger MT, Borden PM, Marvin JS, Looger LL, Khakh BS., A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP, Nat. Commun., 10 (1) (2019) 711. [18] Depaoli MR, Bischof H, Eroglu E, Burgstaller S, Ramadani-Muja J, Rauter T, Schinagl M, Waldeck-Weiermair M, Hay JC, Graier WF, Malli R., Live cell imaging of signaling and metabolic activities, Pharmacol. Ther., 202 (2019) 98–119. [19] Li ES, Saha MS., Optimizing Calcium Detection Methods in Animal Systems: A Sandbox for Synthetic Biology, Biomolecules, 11 (3) (2021) 343. [20] Ghaffari Zaki A, Yiğit EN, Aydın MŞ, Vatandaslar E, Öztürk G, Eroglu E., Genetically Encoded Biosensors Unveil Neuronal Injury Dynamics via Multichromatic ATP and Calcium Imaging, ACS Sens., 9 (3) (2024) 1261-1271. [21] Secilmis M, Altun HY, Pilic J, Erdogan YC, Cokluk Z, Ata BN, Sevimli G, Zaki AG, Yigit EN, Öztürk G, Malli R, Eroglu E., A Co-Culture-Based Multiparametric Imaging Technique to Dissect Local H2O2 Signals with Targeted HyPer7, Biosensors, 11 (9) (2021) 338. [22] Akerboom J, Carreras Calderón N, Tian L, Wabnig S, Prigge M, Tolö J, Gordus A, Orger M, Severi K, Macklin J, Patel R, Pulver S, Wardill T, Fischer E, Schüler C, Chen TW, Sarkisyan K, Marvin J, Bargmann C, Kim D, Kügler S, Lagnado L, Hegemann P, Gottschalk A, Schreiter E, Looger L., Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics, Front. Mol. Neurosci., 6 (2013) Available at: https://www.frontiersin.org/articles/10.3389/fnmol.2013.00002. Retrieved Oct. 23, 2022. [23] Arai S, Kriszt R, Harada K, Looi LS, Matsuda S, Wongso D, Suo S, Ishiura S, Tseng YH, Raghunath M, Ito T, Tsuboi T, Kitaguchi T., RGB-color intensiometric indicators visualize spatiotemporal dynamics of ATP in single cells, Angew. Chem. Int. Ed Engl., 57 (34) (2018) 10873–10878. [24] Gupta RK, Kuznicki J., Biological and Medical Importance of Cellular Heterogeneity Deciphered by Single-Cell RNA Sequencing, Cells, 9 (8) (2020) 1751. [25] Hastings JF, Latham SL, Kamili A, Wheatley MS, Han JZR, Wong-Erasmus M, Phimmachanh M, Nobis M, Pantarelli C, Cadell AL, O’Donnell YEI, Leong KH, Lynn S, Geng FS, Cui L, Yan S, Achinger-Kawecka J, Stirzaker C, Norris MD, Haber M, Trahair TN, Speleman F, De Preter K, Cowley MJ, Bogdanovic O, Timpson P, Cox TR, Kolch W, Fletcher JI, Fey D, Croucher DR., Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma, Sci. Adv., 9 (9) eabp8314. [26] Handly LN, Yao J, Wollman R., Signal transduction at the single-cell level: Approaches to study the dynamic nature of signaling networks, J. Mol. Biol., 428 (19) (2016) 3669. [27] Mattiazzi Usaj M, Yeung CHL, Friesen H, Boone C, Andrews BJ., Single-cell image analysis to explore cell-to-cell heterogeneity in isogenic populations, Cell Syst., 12 (6) (2021) 608–621. [28] Baysoy A, Bai Z, Satija R, Fan R., The technological landscape and applications of single-cell multi-omics, Nat. Rev. Mol. Cell Biol., 24 (10) (2023) 695–713. [29] Altun HY, Secilmis M, Caglar TA, Vatandaslar E, Öztürk G, Vilain S, Eroglu E., Visualizing H2O2 and NO in endothelial cells: strategies and pitfalls. bioRxiv, Available at: https://www.biorxiv.org/content/10.1101/2023.02.15.528776v1. Retrieved Feb. 16, 2023. [30] Shankaran H, Wiley HS, Resat H., Receptor downregulation and desensitization enhance the information processing ability of signalling receptors, BMC Syst. Biol., 1 (2007) 48. [31] Rodríguez-Rodríguez R, Yarova P, Winter P, Dora K., Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in pressurized rat small mesenteric arteries, Br. J. Pharmacol., 158 (6) (2009) 1609–1620. [32] Woolf PJ, Linderman JJ., Untangling Ligand Induced Activation and Desensitization of G-Protein–Coupled Receptors, Biophys. J., 84 (1) (2003) 3–13.
Yıl 2024, Cilt: 45 Sayı: 2, 360 – 365, 30.06.2024
Emrah Eroğlu
https://doi.org/10.17776/csj.1462654
Öz Proje Numarası EMBO IG-5322-2023
Kaynakça [1] Arcuino G, Lin JHC, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M. Intercellular calcium signaling mediated by point-source burst release of ATP, Proc. Natl. Acad. Sci., 99 (15) (2002) 9840–9845. [2] Cisneros-Mejorado A, Pérez-Samartín A, Gottlieb M, Matute C. ATP signaling in brain: release, excitotoxicity and potential therapeutic targets, Cell. Mol. Neurobiol., 35 (1) (2015) 1–6. [3] Depaoli MR, Karsten F, Madreiter-Sokolowski CT, Klec C, Gottschalk B, Bischof H, Eroglu E, Waldeck-Weiermair M, Simmen T, Graier WF, Malli R. Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells, Cell Rep., 25 (2) (2018) 501-512. [4] Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F, Wieckowski MR, Pinton P., ATP synthesis and storage, Purinergic Signal., 8 (3) (2012) 343–357. [5] Eersapah V, Hugel S, Schlichter R., High-resolution detection of ATP release from single cultured mouse dorsal horn spinal cord glial cells and its modulation by noradrenaline, Purinergic Signal., 15 (3) (2019) 403–420. [6] Fields RD, Burnstock G., Purinergic signalling in neuron-glia interactions, Nat. Rev. Neurosci., 7 (6) (2006) 423–436. [7] Eroglu E, Saravi SSS, Sorrentino A, Steinhorn B, Michel T., Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods, Proc. Natl. Acad. Sci. U. S. A., 116 (40) (2019) 20210–20217. [8] Eroglu E, Hallström S, Bischof H, Opelt M, Schmidt K, Mayer B, Waldeck-Weiermair M, Graier WF, Malli R., Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells, Nitric Oxide Biol. Chem., 70 (2017) 59–67. [9] Barry VA, Cheek TR., Extracellular ATP triggers two functionally distinct calcium signalling pathways in PC12 cells, J. Cell Sci., 107 ( Pt 2) (1994) 451–462. [10] Burnstock G., Purine and purinergic receptors, Brain Neurosci. Adv., 2 (2018) 2398212818817494. [11] Molcak H, Jiang K, Campbell CJ, Matsubara JA., Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration, Front. Neurosci., 17 (2023) 1216489. [12] Eroglu E, Gottschalk B, Charoensin S, Blass S, Bischof H, Rost R, Madreiter-Sokolowski CT, Pelzmann B, Bernhart E, Sattler W, Hallström S, Malinski T, Waldeck-Weiermair M, Graier WF, Malli R., Development of novel FP-based probes for live-cell imaging of nitric oxide dynamics, Nat. Commun., 7 (1) (2016). [13] Eroglu E, Rost R, Bischof H, Blass S, Schreilechner A, Gottschalk B, Depaoli MR, Klec C, Charoensin S, Madreiter-Sokolowski CT, Ramadani J, Waldeck-Weiermair M, Graier WF, Malli R., Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells, J. Vis. Exp. JoVE, (121) (2017) 55486. [14] Eroglu E, Charoensin S, Bischof H, Ramadani J, Gottschalk B, Depaoli MR, Waldeck-Weiermair M, Graier WF, Malli R., Genetic biosensors for imaging nitric oxide in single cells, Free Radic. Biol. Med., 128 (2018) 50–58. [15] Wu Z, He K, Chen Y, Li H, Pan S, Li B, Liu T, Xi F, Deng F, Wang H, Du J, Jing M, Li Y., A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo, Neuron, 110 (5) (2022) 770-782. [16] Conley JM, Radhakrishnan S, Valentino SA, Tantama M., Imaging extracellular ATP with a genetically-encoded, ratiometric fluorescent sensor, PLoS ONE, 12 (11) (2017) e0187481. [17] Lobas MA, Tao R, Nagai J, Kronschläger MT, Borden PM, Marvin JS, Looger LL, Khakh BS., A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP, Nat. Commun., 10 (1) (2019) 711. [18] Depaoli MR, Bischof H, Eroglu E, Burgstaller S, Ramadani-Muja J, Rauter T, Schinagl M, Waldeck-Weiermair M, Hay JC, Graier WF, Malli R., Live cell imaging of signaling and metabolic activities, Pharmacol. Ther., 202 (2019) 98–119. [19] Li ES, Saha MS., Optimizing Calcium Detection Methods in Animal Systems: A Sandbox for Synthetic Biology, Biomolecules, 11 (3) (2021) 343. [20] Ghaffari Zaki A, Yiğit EN, Aydın MŞ, Vatandaslar E, Öztürk G, Eroglu E., Genetically Encoded Biosensors Unveil Neuronal Injury Dynamics via Multichromatic ATP and Calcium Imaging, ACS Sens., 9 (3) (2024) 1261-1271. [21] Secilmis M, Altun HY, Pilic J, Erdogan YC, Cokluk Z, Ata BN, Sevimli G, Zaki AG, Yigit EN, Öztürk G, Malli R, Eroglu E., A Co-Culture-Based Multiparametric Imaging Technique to Dissect Local H2O2 Signals with Targeted HyPer7, Biosensors, 11 (9) (2021) 338. [22] Akerboom J, Carreras Calderón N, Tian L, Wabnig S, Prigge M, Tolö J, Gordus A, Orger M, Severi K, Macklin J, Patel R, Pulver S, Wardill T, Fischer E, Schüler C, Chen TW, Sarkisyan K, Marvin J, Bargmann C, Kim D, Kügler S, Lagnado L, Hegemann P, Gottschalk A, Schreiter E, Looger L., Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics, Front. Mol. Neurosci., 6 (2013) Available at: https://www.frontiersin.org/articles/10.3389/fnmol.2013.00002. Retrieved Oct. 23, 2022. [23] Arai S, Kriszt R, Harada K, Looi LS, Matsuda S, Wongso D, Suo S, Ishiura S, Tseng YH, Raghunath M, Ito T, Tsuboi T, Kitaguchi T., RGB-color intensiometric indicators visualize spatiotemporal dynamics of ATP in single cells, Angew. Chem. Int. Ed Engl., 57 (34) (2018) 10873–10878. [24] Gupta RK, Kuznicki J., Biological and Medical Importance of Cellular Heterogeneity Deciphered by Single-Cell RNA Sequencing, Cells, 9 (8) (2020) 1751. [25] Hastings JF, Latham SL, Kamili A, Wheatley MS, Han JZR, Wong-Erasmus M, Phimmachanh M, Nobis M, Pantarelli C, Cadell AL, O’Donnell YEI, Leong KH, Lynn S, Geng FS, Cui L, Yan S, Achinger-Kawecka J, Stirzaker C, Norris MD, Haber M, Trahair TN, Speleman F, De Preter K, Cowley MJ, Bogdanovic O, Timpson P, Cox TR, Kolch W, Fletcher JI, Fey D, Croucher DR., Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma, Sci. Adv., 9 (9) eabp8314. [26] Handly LN, Yao J, Wollman R., Signal transduction at the single-cell level: Approaches to study the dynamic nature of signaling networks, J. Mol. Biol., 428 (19) (2016) 3669. [27] Mattiazzi Usaj M, Yeung CHL, Friesen H, Boone C, Andrews BJ., Single-cell image analysis to explore cell-to-cell heterogeneity in isogenic populations, Cell Syst., 12 (6) (2021) 608–621. [28] Baysoy A, Bai Z, Satija R, Fan R., The technological landscape and applications of single-cell multi-omics, Nat. Rev. Mol. Cell Biol., 24 (10) (2023) 695–713. [29] Altun HY, Secilmis M, Caglar TA, Vatandaslar E, Öztürk G, Vilain S, Eroglu E., Visualizing H2O2 and NO in endothelial cells: strategies and pitfalls. bioRxiv, Available at: https://www.biorxiv.org/content/10.1101/2023.02.15.528776v1. Retrieved Feb. 16, 2023. [30] Shankaran H, Wiley HS, Resat H., Receptor downregulation and desensitization enhance the information processing ability of signalling receptors, BMC Syst. Biol., 1 (2007) 48. [31] Rodríguez-Rodríguez R, Yarova P, Winter P, Dora K., Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in pressurized rat small mesenteric arteries, Br. J. Pharmacol., 158 (6) (2009) 1609–1620. [32] Woolf PJ, Linderman JJ., Untangling Ligand Induced Activation and Desensitization of G-Protein–Coupled Receptors, Biophys. J., 84 (1) (2003) 3–13. Toplam 32 adet kaynakça vardır.
Ayrıntılar Birincil Dil İngilizce Konular Sinyal İletimi Bölüm Natural Sciences Yazarlar Emrah Eroğlu ISTANBUL MEDIPOL UNIVERSITY 0000-0002-9373-0808 Türkiye
Proje Numarası EMBO IG-5322-2023 Yayımlanma Tarihi 30 Haziran 2024 Gönderilme Tarihi 1 Nisan 2024 Kabul Tarihi 7 Haziran 2024 Yayımlandığı Sayı Yıl 2024Cilt: 45 Sayı: 2
Kaynak Göster APA Eroğlu, E. (2024). Multispectral Imaging and Single-Cell Analysis with Genetically Encoded Biosensors Unveil Complex Interactions between Extracellular ATP and Intracellular Calcium. Cumhuriyet Science Journal, 45(2), 360-365. https://doi.org/10.17776/csj.1462654
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