Dental enamel cells express functional SOCE channels

Meerim K. Nurbaeva; Miriam Eckstein; Axel R. Concepcion; Charles E. Smith; Sonal Srikanth; Michael L. Paine; Yousang Gwack; Michael J. Hubbard; Stefan Feske; Rodrigo S. Lacruz

doi:10.1038/srep15803

Dental enamel cells express functional SOCE channels

Meerim K. Nurbaeva, Miriam Eckstein, Axel R. Concepcion, Charles E. Smith, Sonal Srikanth, Michael L. Paine, Yousang Gwack, Michael J. Hubbard, Stefan Feske, Rodrigo S. Lacruz

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Dental enamel formation requires large quantities of Ca 2+ yet the mechanisms mediating Ca 2+ dynamics in enamel cells are unclear. Store-operated Ca 2+ entry (SOCE) channels are important Ca 2+ influx mechanisms in many cells. SOCE involves release of Ca 2+ from intracellular pools followed by Ca 2+ entry. The best-characterized SOCE channels are the Ca 2+ release-activated Ca 2+ (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca 2+ uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP 3 R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP 3 Rs are the main ER Ca 2+ release mechanism. Passive depletion of ER Ca 2+ stores with thapsigargin resulted in a significant raise in [Ca 2+ ] i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca 2+ entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca 2+ uptake in enamel formation.

Original language	English (US)
Article number	15803
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep15803
State	Published - Oct 30 2015

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@article{ef520e106d6d4b659e44683ca0501fc5,

title = "Dental enamel cells express functional SOCE channels",

abstract = "Dental enamel formation requires large quantities of Ca 2+ yet the mechanisms mediating Ca 2+ dynamics in enamel cells are unclear. Store-operated Ca 2+ entry (SOCE) channels are important Ca 2+ influx mechanisms in many cells. SOCE involves release of Ca 2+ from intracellular pools followed by Ca 2+ entry. The best-characterized SOCE channels are the Ca 2+ release-activated Ca 2+ (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca 2+ uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP 3 R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP 3 Rs are the main ER Ca 2+ release mechanism. Passive depletion of ER Ca 2+ stores with thapsigargin resulted in a significant raise in [Ca 2+ ] i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca 2+ entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca 2+ uptake in enamel formation.",

author = "Nurbaeva, {Meerim K.} and Miriam Eckstein and Concepcion, {Axel R.} and Smith, {Charles E.} and Sonal Srikanth and Paine, {Michael L.} and Yousang Gwack and Hubbard, {Michael J.} and Stefan Feske and Lacruz, {Rodrigo S.}",

note = "Funding Information: This work was funded by NIH/NIDCR K99/R00 award (DE022799) to RSL, NIH grant AI097302 to SF, NIH/NIDCR (DE019629) to MLP, NIH grant AI083432 to YG, and by the Melbourne Research Unit for Facial Disorders to MJH. ARC is funded by a postdoctoral fellowship from the Alfonso Martin Escudero Foundation. The authors would like to thank the two anonymous reviewers for their comments which helped improve this manuscript. Finally, the authors would like to thank Johanna Warshaw for help with Figure 5.",

year = "2015",

month = oct,

day = "30",

doi = "10.1038/srep15803",

language = "English (US)",

volume = "5",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Dental enamel cells express functional SOCE channels

AU - Nurbaeva, Meerim K.

AU - Eckstein, Miriam

AU - Concepcion, Axel R.

AU - Smith, Charles E.

AU - Srikanth, Sonal

AU - Paine, Michael L.

AU - Gwack, Yousang

AU - Hubbard, Michael J.

AU - Feske, Stefan

AU - Lacruz, Rodrigo S.

N1 - Funding Information: This work was funded by NIH/NIDCR K99/R00 award (DE022799) to RSL, NIH grant AI097302 to SF, NIH/NIDCR (DE019629) to MLP, NIH grant AI083432 to YG, and by the Melbourne Research Unit for Facial Disorders to MJH. ARC is funded by a postdoctoral fellowship from the Alfonso Martin Escudero Foundation. The authors would like to thank the two anonymous reviewers for their comments which helped improve this manuscript. Finally, the authors would like to thank Johanna Warshaw for help with Figure 5.

PY - 2015/10/30

Y1 - 2015/10/30

N2 - Dental enamel formation requires large quantities of Ca 2+ yet the mechanisms mediating Ca 2+ dynamics in enamel cells are unclear. Store-operated Ca 2+ entry (SOCE) channels are important Ca 2+ influx mechanisms in many cells. SOCE involves release of Ca 2+ from intracellular pools followed by Ca 2+ entry. The best-characterized SOCE channels are the Ca 2+ release-activated Ca 2+ (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca 2+ uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP 3 R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP 3 Rs are the main ER Ca 2+ release mechanism. Passive depletion of ER Ca 2+ stores with thapsigargin resulted in a significant raise in [Ca 2+ ] i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca 2+ entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca 2+ uptake in enamel formation.

AB - Dental enamel formation requires large quantities of Ca 2+ yet the mechanisms mediating Ca 2+ dynamics in enamel cells are unclear. Store-operated Ca 2+ entry (SOCE) channels are important Ca 2+ influx mechanisms in many cells. SOCE involves release of Ca 2+ from intracellular pools followed by Ca 2+ entry. The best-characterized SOCE channels are the Ca 2+ release-activated Ca 2+ (CRAC) channels. As patients with mutations in the CRAC channel genes STIM1 and ORAI1 show abnormal enamel mineralization, we hypothesized that CRAC channels might be an important Ca 2+ uptake mechanism in enamel cells. Investigating primary murine enamel cells, we found that key components of CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the maturation stage of enamel development. Furthermore, inositol 1,4,5-trisphosphate receptor (IP 3 R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP 3 Rs are the main ER Ca 2+ release mechanism. Passive depletion of ER Ca 2+ stores with thapsigargin resulted in a significant raise in [Ca 2+ ] i consistent with SOCE. In cells pre-treated with the CRAC channel blocker Synta-66 Ca 2+ entry was significantly inhibited. These data demonstrate that enamel cells have SOCE mediated by CRAC channels and implicate them as a mechanism for Ca 2+ uptake in enamel formation.

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U2 - 10.1038/srep15803

DO - 10.1038/srep15803

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SN - 2045-2322

VL - 5

JO - Scientific reports

JF - Scientific reports

M1 - 15803

ER -

Dental enamel cells express functional SOCE channels

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