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 (IP3R) but not ryanodine receptor (RyR) expression was high in enamel cells suggesting that IP3Rs 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.
authors.affiliation: Dept. Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA.
authors.forename: Meerim K
authors.initials: MK
authors.lastname: Nurbaeva
authors.affiliation: Dept. Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eckstein
authors.affiliation: Dept. of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Axel R
authors.initials: AR
authors.lastname: Concepcion
authors.affiliation: Department of Anatomy &Cell Biology, McGill University, Facility for Electron Microscopy Research, Montreal, H3A 2B2, Canada.|Faculty of Dentistry, McGill University, Facility for Electron Microscopy Research, Montreal, H3A 2B2, Canada.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Dept. of Physiology, University of California, Los Angeles, 53-266 CHS, 10833 Le Conte Avenue, Los Angeles, California, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Srikanth
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California, CSA 135-HSC 9062, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Paine
authors.affiliation: Dept. of Physiology, University of California, Los Angeles, 53-266 CHS, 10833 Le Conte Avenue, Los Angeles, California, USA.
authors.forename: Yousang
authors.initials: Y
authors.lastname: Gwack
authors.affiliation: Departments of Paediatrics and Pharmacology, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hubbard
authors.affiliation: Dept. of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
authors.affiliation: Dept. Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Lacruz
mesh_terms: D000565:Ameloblasts / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003743:Dental Enamel / Q000166:cytology / Q000378:metabolism*; D016257:Fura-2 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071740:ORAI1 Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: C506948:Atp2a2 protein, rat; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D019837:Ryanodine Receptor Calcium Release Channel; C560435:STIM2 protein, rat; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D016257:Fura-2