SLC26A Gene Family Participate in pH Regulation during Enamel Maturation

PLoS One. 2015 Dec 15;10(12):e0144703. doi: 10.1371/journal.pone.0144703. eCollection 2015.


The bicarbonate transport activities of Slc26a1, Slc26a6 and Slc26a7 are essential to physiological processes in multiple organs. Although mutations of Slc26a1, Slc26a6 and Slc26a7 have not been linked to any human diseases, disruption of Slc26a1, Slc26a6 or Slc26a7 expression in animals causes severe dysregulation of acid-base balance and disorder of anion homeostasis. Amelogenesis, especially the enamel formation during maturation stage, requires complex pH regulation mechanisms based on ion transport. The disruption of stage-specific ion transporters frequently results in enamel pathosis in animals. Here we present evidence that Slc26a1, Slc26a6 and Slc26a7 are highly expressed in rodent incisor ameloblasts during maturation-stage tooth development. In maturation-stage ameloblasts, Slc26a1, Slc26a6 and Slc26a7 show a similar cellular distribution as the cystic fibrosis transmembrane conductance regulator (Cftr) to the apical region of cytoplasmic membrane, and the distribution of Slc26a7 is also seen in the cytoplasmic/subapical region, presumably on the lysosomal membrane. We have also examined Slc26a1 and Slc26a7 null mice, and although no overt abnormal enamel phenotypes were observed in Slc26a1-/- or Slc26a7-/- animals, absence of Slc26a1 or Slc26a7 results in up-regulation of Cftr, Ca2, Slc4a4, Slc4a9 and Slc26a9, all of which are involved in pH homeostasis, indicating that this might be a compensatory mechanism used by ameloblasts cells in the absence of Slc26 genes. Together, our data show that Slc26a1, Slc26a6 and Slc26a7 are novel participants in the extracellular transport of bicarbonate during enamel maturation, and that their functional roles may be achieved by forming interaction units with Cftr.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ameloblasts / metabolism
  • Amelogenesis / genetics
  • Animals
  • Anion Transport Proteins / genetics*
  • Anion Transport Proteins / metabolism
  • Blotting, Western
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Dental Enamel / growth & development*
  • Dental Enamel / metabolism
  • Dental Enamel / ultrastructure
  • Dentin / metabolism
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Hydrogen-Ion Concentration
  • Mandible / diagnostic imaging
  • Mice
  • Multigene Family*
  • Phenotype
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Spectrometry, X-Ray Emission
  • Up-Regulation / genetics
  • X-Ray Microtomography


  • Anion Transport Proteins
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator