International Journal of Oral Biology

  • 제46권3호
  • /
  • Pages.134-139
  • /
  • 2021
  • /
  • 1226-7155(pISSN)
  • /
  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
권호 표지
DOI QR코드

DOI QR Code

Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells

  • Kang, Jung Yun (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry) ;
  • Kang, Namju (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry) ;
  • Yang, Yu-Mi (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry)
  • 투고 : 2021.09.01
  • 심사 : 2021.09.07
  • 발행 : 2021.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Under physiological conditions, calcium (Ca2+) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2-/-) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2-/- mice. Furthermore, the response of Ca2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2-/- mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.

키워드

과제정보

이 논문은 정부(과학기술정보통신부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임(NRF-2015R1D1A1A01057277, NRF-2020R1A2C1004942).

참고문헌

  1. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000;1:11-21. doi: 10.1038/35036035.
  2. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003;4:517-29. doi: 10.1038/nrm1155.
  3. Chvanov M, Voronina S, Criddle DN, Tepikin AV. The role of Ca2+ signalling in the physiology and pathophysiology of exocrine pancreas. Curr Opin Physiol 2020;17:96-105. doi: 10.1016/j.cophys.2020.07.013.
  4. Mori MX, Itsuki K, Hase H, Sawamura S, Kurokawa T, Mori Y, Inoue R. Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway. Front Pharmacol 2015;6:22. doi: 10.3389/fphar.2015.00022.
  5. Petersen OH, Tepikin AV. Polarized calcium signaling in exocrine gland cells. Annu Rev Physiol 2008;70:273-99. doi: 10.1146/annurev.physiol.70.113006.100618.
  6. Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 1997;386:284-8. doi: 10.1038/386284a0.
  7. Worley PF, Zeng W, Huang G, Kim JY, Shin DM, Kim MS, Yuan JP, Kiselyov K, Muallem S. Homer proteins in Ca2+ signaling by excitable and non-excitable cells. Cell Calcium 2007;42:363-71. doi: 10.1016/j.ceca.2007.05.007.
  8. Smani T, Dionisio N, Lopez JJ, Berna-Erro A, Rosado JA. Cytoskeletal and scaffolding proteins as structural and functional determinants of TRP channels. Biochim Biophys Acta 2014;1838:658-64. doi: 10.1016/j.bbamem.2013.01.009.
  9. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 2003;114:777-89. doi: 10.1016/s0092-8674(03)00716-5.
  10. Shin DM, Dehoff M, Luo X, Kang SH, Tu J, Nayak SK, Ross EM, Worley PF, Muallem S. Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities. J Cell Biol 2003;162:293-303. doi: 10.1083/jcb.200210109.
  11. Kang N, Kang JY, Shin DM, Yang YM. Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells. Int J Oral Biol 2020;45:58-63. doi: 10.11620/IJOB.2020.45.2.58.
  12. Yang YM, Lee J, Jo H, Park S, Chang I, Muallem S, Shin DM. Homer2 protein regulates plasma membrane Ca2+-ATPase-mediated Ca2+ signaling in mouse parotid gland acinar cells. J Biol Chem 2014;289:24971-9. doi: 10.1074/jbc.M114.577221.
  13. Stiber JA, Tabatabaei N, Hawkins AF, Hawke T, Worley PF, Williams RS, Rosenberg P. Homer modulates NFAT-dependent signaling during muscle differentiation. Dev Biol 2005;287:213-24. doi: 10.1016/j.ydbio.2005.06.030.
  14. Huang GN, Huso DL, Bouyain S, Tu J, McCorkell KA, May MJ, Zhu Y, Lutz M, Collins S, Dehoff M, Kang S, Whartenby K, Powell J, Leahy D, Worley PF. NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins. Science 2008;319:476-81. doi: 10.1126/science.1151227.
  15. Son A, Kang N, Oh SY, Kim KW, Muallem S, Yang YM, Shin DM. Homer2 and Homer3 modulate RANKL-induced NFATc1 signaling in osteoclastogenesis and bone metabolism. J Endocrinol 2019;242:241-9. doi: 10.1530/JOE-19-0123.
  16. Kang JY, Kang N, Shin DM, Yang YM. Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice. Int J Oral Biol 2020;45:126-33. doi: 10.11620/IJOB.2020.45.3.126.
  17. DeHaven WI, Smyth JT, Boyles RR, Bird GS, Putney JW Jr. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem 2008;283:19265-73. doi: 10.1074/jbc.M801535200.
  18. Liao Y, Erxleben C, Abramowitz J, Flockerzi V, Zhu MX, Armstrong DL, Birnbaumer L. Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc Natl Acad Sci U S A 2008;105:2895-900. doi: 10.1073/pnas.0712288105.
  19. He X, Li S, Liu B, Susperreguy S, Formoso K, Yao J, Kang J, Shi A, Birnbaumer L, Liao Y. Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries. Proc Natl Acad Sci U S A 2017;114:E4582-91. doi: 10.1073/pnas.1621384114.
  20. Ambudkar IS. Calcium signalling in salivary gland physiology and dysfunction. J Physiol 2016;594:2813-24. doi: 10.1113/JP271143.