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http://dx.doi.org/10.11620/IJOB.2020.45.2.58

Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells  

Kang, Namju (Department of Oral Biology, Yonsei University College of Dentistry)
Kang, Jung Yun (Department of Oral Biology, Yonsei University College of Dentistry)
Shin, Dong Min (Department of Oral Biology, Yonsei University College of Dentistry)
Yang, Yu-Mi (Department of Oral Biology, Yonsei University College of Dentistry)
Publication Information
International Journal of Oral Biology / v.45, no.2, 2020 , pp. 58-63 More about this Journal
Abstract
The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca2+) signaling mechanisms such as increases in the intracellular Ca2+ concentration ([Ca2+]i) via storeoperated Ca2+ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP3Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca2+ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca2+ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2-/-) markedly decreased the amplitude of [Ca2+]i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca2+]i oscillations showed no difference between wild-type and Homer2-/- mice. Homer2-/- mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca2+]i concentration and secretion of saliva in mouse parotid gland acinar cells.
Keywords
Calcium signaling; Salivation; Acinar cells; Physiological phenomena;
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1 Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev 2006;86:369-408. doi: 10.1152/physrev.00004.2005.   DOI
2 Lee MG, Ohana E, Park HW, Yang D, Muallem S. Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion. Physiol Rev 2012;92:39-74. doi: 10.1152/physrev.00011.2011.   DOI
3 Ambudkar IS. Ca$^{2+}$ signaling and regulation of fluid secretion in salivary gland acinar cells. Cell Calcium 2014;55:297-305. doi: 10.1016/j.ceca.2014.02.009.   DOI
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 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.   DOI
8 Worley PF, Zeng W, Huang G, Kim JY, Shin DM, Kim MS, Yuan JP, Kiselyov K, Muallem S. Homer proteins in Ca$^{2+}$ signaling by excitable and non-excitable cells. Cell Calcium 2007;42:363-71. doi: 10.1016/j.ceca.2007.05.007.   DOI
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.   DOI
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.   DOI
11 Yang YM, Lee J, Jo H, Park S, Chang I, Muallem S, Shin DM. Homer2 protein regulates plasma membrane Ca$^{2+}$-ATPase-mediated Ca$^{2+}$- signaling in mouse parotid gland acinar cells. J Biol Chem 2014;289:24971-9. doi: 10.1074/jbc.M114.577221.   DOI
12 Stiber JA, Tabatabaei N, Hawkins AF, Hawke T, Worley PF, Williams RS, Rosenberg P. Homer modulates NFATdependent signaling during muscle differentiation. Dev Biol 2005;287:213-24. doi: 10.1016/j.ydbio.2005.06.030.   DOI
13 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.   DOI
14 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.   DOI
15 Berridge MJ. Calciumoscillations. J Biol Chem 1990;265:9583-6.   DOI
16 Sneyd J, Han JM, Wang L, Chen J, Yang X, Tanimura A, Sanderson MJ, Kirk V, Yule DI. On the dynamical structure of calcium oscillations. Proc Natl Acad Sci U S A 2017;114:1456-61. doi: 10.1073/pnas.1614613114.   DOI
17 Smedler E, Uhlen P. Frequency decoding of calcium oscillations. Biochim Biophys Acta 2014;1840:964-9. doi: 10.1016/j.bbagen.2013.11.015.   DOI
18 Song S, Li J, Zhu L, Cai L, Xu Q, Ling C, Su Y, Hu Q. Irregular Ca(2+) oscillations regulate transcription via cumulative spike duration and spike amplitude. J Biol Chem 2012;287:40246-55. doi: 10.1074/jbc.M112.417154.   DOI
19 Gaspers LD, Bartlett PJ, Politi A, Burnett P, Metzger W, Johnston J, Joseph SK, Hofer T, Thomas AP. Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations. Cell Rep 2014;9:1209-18. doi: 10.1016/j.celrep.2014.10.033.   DOI
20 Ambudkar IS. Calcium signalling in salivary gland physiology and dysfunction. J Physiol 2016;594:2813-24. doi: 10.1113/JP271143.   DOI
21 Samanta K, Parekh AB. Spatial Ca2+ profiling: decrypting the universal cytosolic Ca2+ oscillation. J Physiol 2017;595:3053-62. doi: 10.1113/JP272860.   DOI
22 Li Q, Luo X, Muallem S. Functional mapping of Ca2+ signaling complexes in plasma membrane microdomains of polarized cells. J Biol Chem 2004;279:27837-40. doi: 10.1074/jbc.C400184200.   DOI
23 Kasai H, Augustine GJ. Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas. Nature 1990;348:735-8. doi: 10.1038/348735a0.   DOI
24 Kasai H, Li YX, Miyashita Y. Subcellular distribution of Ca2+ release channels underlying Ca2+ waves and oscillations in exocrine pancreas. Cell 1993;74:669-77. doi: 10.1016/0092-8674(93)90514-q.   DOI
25 Giovannucci DR, Bruce JI, Straub SV, Arreola J, Sneyd J, Shuttleworth TJ, Yule DI. Cytosolic Ca(2+) and Ca(2+)-activated Cl(-) current dynamics: insights from two functionally distinct mouse exocrine cells. J Physiol 2002;540(Pt 2):469-84. doi: 10.1113/jphysiol.2001.013453.   DOI
26 Gray PT. Oscillations of free cytosolic calcium evoked by cholinergic and catecholaminergic agonists in rat parotid acinar cells. J Physiol 1988;406:35-53. doi: 10.1113/jphysiol.1988.sp017367.   DOI
27 Thorn P, Lawrie AM, Smith PM, Gallacher DV, Petersen OH. Local and global cytosolic Ca2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate. Cell 1993;74:661-8. doi: 10.1016/0092-8674(93)90513-p.   DOI
28 Larina O, Thorn P. Ca2+ dynamics in salivary acinar cells: distinct morphology of the acinar lumen underlies nearsynchronous global Ca2+ responses. J Cell Sci 2005;118(Pt 18):4131-9. doi: 10.1242/jcs.02533.   DOI
29 Bernfeld P. Enzymes of starch degradation and synthesis. Adv Enzymol Relat Subj Biochem 1951;12:379-428. doi: 10.1002/9780470122570.ch7.
30 Choi JH, Jo H, Hong JH, Lee SI, Shin DM. Alteration of expression of Ca2+ signaling proteins and adaptation of Ca2+ signaling in SERCA2+/- mouse parotid acini. Yonsei Med J 2008;49:311-21. doi: 10.3349/ymj.2008.49.2.311.   DOI
31 Park S, Lee SI, Shin DM. Role of regulators of g-protein signaling 4 in ca signaling in mouse pancreatic acinar cells. Korean J Physiol Pharmacol 2011;15:383-8. doi: 10.4196/kjpp.2011.15.6.383.   DOI
32 Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 1997;386:855-8. doi: 10.1038/386855a0.   DOI
33 Gaspers LD, Thomas AP. Calcium signaling in liver. Cell Calcium 2005;38:329-42. doi: 10.1016/j.ceca.2005.06.009.   DOI