Enamel cell biology – how is bulk calcium handled safely?

Project Details

Calcium plays numerous key roles in cells from their birth through to their death. Consequently, there is much medical interest in manipulating calcium-dependent activities, for example to help keep damaged cells alive in neurodegenerative diseases or hastening the death of renegade cells in cancer. Enamel-forming cells hold interest in this regard as a calcium-savvy cell type that handles a lot of calcium (for mineralisation of dental enamel) without succumbing to the potentially cytotoxic effects of excessive intracellular calcium. To learn how enamel cells survive such a calcium onslaught, we developed microscale proteomic approaches and characterised enamel epithelial cells from developing teeth in neonatal rats and mice. This information was used to investigate the mechanistic basis of calcium transport across enamel cells. Our findings contradicted the classical "calcium ferry" dogma and led to development of a new paradigm for transcellular calcium transport that we've named "calcium transcytosis". Increasingly, it appears this organelle-based mechanism could be more generally applicable across biology. This advance in turn necessitates a reevaluation of the biological roles of calbindins (see Calbindin Project).


Dr Jon Mangum, Project co-leader

Research Outcomes

  • Nurbaeva MK, Eckstein M, Devotta A, Saint-Jeannet JP, Yule DI, Hubbard MJ, Lacruz RS: Evidence That Calcium Entry Into Calcium-Transporting Dental Enamel Cells Is Regulated by Cholecystokinin, Acetylcholine and ATP. Front Physiol. 2018; 9, 801. (PMID: 30013487)
  • Kirkham J, Brookes SJ, Diekwisch TGH, Margolis HC, Berdal A, Hubbard MJ. Enamel Research: Priorities and Future Directions. Front Physiol. 2017: 8, 513. (PMID: 28775693)
  • Mangum JE, Kon JC, Hubbard MJ. Proteomic Analysis of Dental Tissue Microsamples. Methods Mol Biol. 2017: 1537, 461-479. (PMID: 27924612)
  • Nurbaeva MK, Eckstein M, Concepcion AR, Smith CE, Srikanth S, Paine ML, Gwack Y, Hubbard MJ, Feske S, Lacruz RS. Dental enamel cells express functional SOCE channels. Sci Rep 2015; 5: 15803; doi: 10.1038/srep15803 (PMID: 26515404)
  • Lacruz RS, Smith CE, Kurtz I, Hubbard MJ, Paine ML. New Paradigms on the Transport Functions of Maturation-stage Ameloblasts. J Dent Res. 2013 Feb;92(2):122-9. (PMID: 23242231)
  • Lacruz, RS, Smith CE, Bringas P, Chen YB, Smith SM, Snead ML, Kurtz I, Hacia JG, Hubbard MJ, Paine ML. (2012) Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling. J. Cell Physiol. 227, 2264-2275 (PMID: 21809343)
  • Hubbard MJ, McHugh NJ, Mangum JE. (2011) Exclusion of all three calbindins from a calcium-ferry role in rat enamel cells. Eur. J. Oral Sci. 119 (Suppl. 1), 112-119 (PMID: 22243236)
  • Lacruz RS, Smith CE, Chen Y, Hubbard MJ, Hacia JG, Paine ML. (2011) Gene expression analysis of early and late maturation stage rat enamel organ. Eur. J. Oral Sci. (119 (Suppl. 1), 149-157 (PMID: 21809343)
  • Mangum JE, Kon JC, Hubbard MJ. (2010) Proteomic analysis of dental tissue microsamples. Methods Mol. Biol. 666,  309-325 (PMID: 20717792)
  • Mangum JE, Veith PD, Reynolds EC, Hubbard MJ. (2006) Towards second-generation proteome analysis of murine enamel-forming cells. Eur. J. Oral Sci. 114, 259-265 (PMID:16674695)
  • Turnbull CI, Looi K, Mangum JE, Meyer M, Sayer RJ, Hubbard MJ. (2004) Calbindin-independence of calcium transport in developing teeth contradicts the calcium-ferry dogma. J. Biol. Chem. 279, 55850-55854 (PMID: 15494408)
  • Hubbard MJ, Kon JC. (2002) Proteomic analysis of dental tissues. J. Chromatogr. B, 771, 211-220 (PMID: 12016000)
  • Franklin IK, Winz RA, Hubbard MJ. (2001) Endoplasmic reticulum Ca2+-ATPase pump is up-regulated in calcium-transporting dental enamel cells: A non-housekeeping role for SERCA2b. Biochem. J., 358, 217-224 (PMID: 11485570)
  • Hubbard MJ, Faught MJ, Carlisle BH, Stockwell PA. (2001) ToothPrint, a proteomic database for dental tissues. Proteomics 1, 132-135 (PMID: 11680893)
  • Hubbard MJ. (2000) Calcium transport across the dental enamel epithelium. Crit. Rev. Oral Biol. Med., 11, 437-466 (PMID: 11132765)
  • Hubbard MJ. (1998) Proteomic analysis of enamel cells from developing rat teeth. Big returns from a small tissue. Electrophoresis, 19, 1891-1900 (PMID: 9740049)
  • Hubbard MJ. (1998) Enamel cell biology. Towards a comprehensive biochemical understanding. Conn. Tissue Res., 39, 17-32 (PMID: 11063013)
  • Hubbard MJ. (1996) Abundant calcium homeostasis machinery in rat dental enamel cells. Up-regulation of calcium store proteins during enamel hypermineralization implicates the endoplasmic reticulum in calcium transcytosis. Eur. J. Biochem., 239, 611-623 (PMID: 877470)
  • Hubbard MJ. (1995) Calbindin28kDa and calmodulin are hyperabundant in rat dental enamel cells. Identification of the protein phosphatase  calcineurin as a principal calmodulin target and of a secretion-related role for calbindin 28kDa. Eur. J. Biochem., 230, 68-79 (PMID: 7601126)

Research Group

Faculty Research Themes

Child Health

School Research Themes

Key Contact

For further information about this research, please contact the research group leader.

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