Regulatory mechanisms of the store-operated Ca2+ entry through Orai1 and STIM1 by an adaptor protein in non-excitable cells
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초록
Store-operated Ca2+ entry (SOCE) represents one of the major Ca2+ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca2+ homeostasis. The Ca2+ releaseactivated Ca2+ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca2+ signaling through the activation of CRAC channels in non-excitable cells still remain unknown. In the present study, we investigated the role of Homer2 in the process of Ca2+ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca2+ entry by thapsigargin-mediated Ca2+ store depletion remarkably decreased in pancreatic acinar cells of Homer2–/– mice, as compared to wild-type cells. It also showed critical differences in regulated patterns by the specific blockers of SOCE in pancreatic acinar cells of Homer2–/– mice. The response to Ca2+ entry by the depletion in Ca2+ store markedly increased in the cellular overexpression of Orai1 and STIM1 as compared to the overexpression of Homer2 in cells; however, this response was remarkably inhibited by the overexpression of Orai1, STIM1, and Homer2. These results suggest that Homer2 has a critical role in the regulatory action of SOCE activity and the interactions between CRAC channels.
Abstract
Store-operated Ca2+ entry (SOCE) represents one of the major Ca2+ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca2+ homeostasis. The Ca2+ releaseactivated Ca2+ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca2+ signaling through the activation of CRAC channels in non-excitable cells still remain unknown. In the present study, we investigated the role of Homer2 in the process of Ca2+ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca2+ entry by thapsigargin-mediated Ca2+ store depletion remarkably decreased in pancreatic acinar cells of Homer2–/– mice, as compared to wild-type cells. It also showed critical differences in regulated patterns by the specific blockers of SOCE in pancreatic acinar cells of Homer2–/– mice. The response to Ca2+ entry by the depletion in Ca2+ store markedly increased in the cellular overexpression of Orai1 and STIM1 as compared to the overexpression of Homer2 in cells; however, this response was remarkably inhibited by the overexpression of Orai1, STIM1, and Homer2. These results suggest that Homer2 has a critical role in the regulatory action of SOCE activity and the interactions between CRAC channels.
참고문헌 (32)
- Michael J. Berridge, "Calcium signalling: dynamics, homeostasis and remodelling", Nature Reviews Molecular Cell Biology, 4(7), pp.517~529 (2003), Springer Science and Business Media LLC[DOI]
- Anant B. Parekh, "Store-Operated Calcium Channels", Physiological Reviews, 85(2), pp.757~810 (2005), American Physiological Society[DOI]
- Shenyuan L. Zhang, "STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane", Nature, 437(7060), pp.902~905 (2005), Springer Science and Business Media LLC[DOI]
- Christine Peinelt, "Amplification of CRAC current by STIM1 and CRACM1 (Orai1)", Nature Cell Biology, 8(7), pp.771~773 (2006), Springer Science and Business Media LLC[DOI]
- Jonathan Soboloff, "Orai1 and STIM Reconstitute Store-operated Calcium Channel Function", Journal of Biological Chemistry, 281(30), pp.20661~20665 (2006), Elsevier BV[DOI]
- Joseph P. Yuan, "STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels", Nature Cell Biology, 9(6), pp.636~645 (2007), Springer Science and Business Media LLC[DOI]
- Weizhong Zeng, "STIM1 Gates TRPC Channels, but Not Orai1, by Electrostatic Interaction", Molecular Cell, 32(3), pp.439~448 (2008), Elsevier BV[DOI]
- Joseph P. Yuan, "SOAR and the polybasic STIM1 domains gate and regulate Orai channels", Nature Cell Biology, 11(3), pp.337~343 (2009), Springer Science and Business Media LLC[DOI]
- Youjun Wang, "The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels", Science, 330(6000), pp.105~109 (2010), American Association for the Advancement of Science (AAAS)[DOI]
- Natalia Dionisio, "Homer proteins mediate the interaction between STIM1 and Cav1.2 channels", Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1853(5), pp.1145~1153 (2015), Elsevier BV[DOI]
- Kirill Kiselyov, "The N-Terminal Domain of the IP3 Receptor Gates Store-Operated hTrp3 Channels", Molecular Cell, 4(3), pp.423~429 (1999), Elsevier BV[DOI]
- Joseph P Yuan, "Homer Binds TRPC Family Channels and Is Required for Gating of TRPC1 by IP3 Receptors", Cell, 114(6), pp.777~789 (2003), Elsevier BV[DOI]
- P WORLEY, "Homer proteins in Ca2+ signaling by excitable and non-excitable cells", Cell Calcium, 42(4-5), pp.363~371 (2007), Elsevier BV[DOI]
- Isaac Jardin, "Homers regulate calcium entry and aggregation in human platelets: a role for Homers in the association between STIM1 and Orai1", Biochemical Journal, 445(1), pp.29~38 (2012), Portland Press Ltd[DOI]
- P. R. Brakeman, "Homer: a protein that selectively binds metabotropic glutamate receptors", Nature, 386(6622), pp.284~288 (1997), Springer Science and Business Media LLC[DOI]
- Shuping Jia, "Homer binds to Orai1 and TRPC channels in the neointima and regulates vascular smooth muscle cell migration and proliferation", Scientific Reports, 7(1), pp.5075~ (2017), Springer Science and Business Media LLC[DOI]
- Dong Min Shin, "Homer 2 tunes G protein–coupled receptors stimulus intensity by regulating RGS proteins and PLCβ GAP activities", Journal of Cell Biology, 162(2), pp.293~303 (2003), Rockefeller University Press[DOI]
- 강정윤, "Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells", International Journal of Oral Biology, 46(3), pp.134~139 (2021), 대한구강생물학회
- Yu-Mi Yang, "Homer2 Protein Regulates Plasma Membrane Ca2+-ATPase-mediated Ca2+ Signaling in Mouse Parotid Gland Acinar Cells", Journal of Biological Chemistry, 289(36), pp.24971~24979 (2014), Elsevier BV[DOI]
- 강남주, "Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells", International Journal of Oral Biology, 45(2), pp.58~63 (2020), 대한구강생물학회
- Jonathan A. Stiber, "Homer modulates NFAT-dependent signaling during muscle differentiation", Developmental Biology, 287(2), pp.213~224 (2005), Elsevier BV[DOI]
- Guo N. Huang, "NFAT Binding and Regulation of T Cell Activation by the Cytoplasmic Scaffolding Homer Proteins", Science, 319(5862), pp.476~481 (2008), American Association for the Advancement of Science (AAAS)[DOI]
- Aran Son, "Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism", Journal of Endocrinology, 242(3), pp.241~249 (2019), Bioscientifica[DOI]
- 강정윤, "Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice", International Journal of Oral Biology, 45(3), pp.126~133 (2020), 대한구강생물학회[DOI]
- Wei Rao, "Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry", Scientific Reports, 6(1), pp.33975~ (2016), Springer Science and Business Media LLC[DOI]
- Jonathan Soboloff, "STIM proteins: dynamic calcium signal transducers", Nature Reviews Molecular Cell Biology, 13(9), pp.549~565 (2012), Springer Science and Business Media LLC[DOI]
- Jose J. Lopez, "Molecular modulators of store-operated calcium entry", Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1863(8), pp.2037~2043 (2016), Elsevier BV[DOI]
- Karolina Serwach, "Target Molecules of STIM Proteins in the Central Nervous System", Frontiers in Molecular Neuroscience, 13, pp.617422~ (2020), Frontiers Media SA[DOI]
- Ming Wei, "Molecular mechanisms underlying inhibition of STIM1-Orai1-mediated Ca2+ entry induced by 2-aminoethoxydiphenyl borate", Pflügers Archiv - European Journal of Physiology, 468(11-12), pp.2061~2074 (2016), Springer Science and Business Media LLC[DOI]
- Chengsen Tian, "Store-operated CRAC channel inhibitors: opportunities and challenges", Future Medicinal Chemistry, 8(7), pp.817~832 (2016), Future Science Ltd[DOI]
- Wayne I. DeHaven, "Complex Actions of 2-Aminoethyldiphenyl Borate on Store-operated Calcium Entry", Journal of Biological Chemistry, 283(28), pp.19265~19273 (2008), Elsevier BV[DOI]
- David E. Clapham, "The trp ion channel family", Nature Reviews Neuroscience, 2(6), pp.387~396 (2001), Springer Science and Business Media LLC[DOI]