Role of NBCe1 and AE2 in Secretory Ameloblasts

Abstract

The H(+)/base transport processes that control the pH of the microenvironment adjacent to ameloblasts are not currently well-understood. Mice null for the AE2 anion exchanger have abnormal enamel. In addition, persons with mutations in the electrogenic sodium bicarbonate co-transporter NBCe1 and mice lacking NBCe1 have enamel abnormalities. These observations suggest that AE2 and NBCe1 play important roles in amelogenesis. In the present study, we aimed to understand the roles of AE2 and NBCe1 in ameloblasts. Analysis of the data showed that NBCe1 is expressed at the basolateral membrane of secretory ameloblasts, whereas AE2 is expressed at the apical membrane. Transcripts for AE2a and NBCe1-B were detected in RNA isolated from cultured ameloblast-like LS8 cells. Our data are the first evidence that AE2 and NBCe1 are expressed in ameloblasts in vivo in a polarized fashion, thereby providing a mechanism for ameloblast transcellular bicarbonate secretion in the process of enamel formation and maturation.

MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization

“…Furthermore, in the later maturation stage, the enamel matrix pH shifts from acidic to neutral, indicating tight modulation of pH homeostasis (1,4). As previously reported by us and others, ameloblasts play a critical role in regulating pH through various mechanisms, including the buffering system of amelogenin (AMLX) protein (3) and differential ion channel expression in differentiated ameloblasts (5,6). The ion channels, such as anion exchanger 2 (AE2), electrogenic bicarbonate cotransporter 1 (NBCe1), and cystic fibrosis (CF) conductance transmembrane regulator (CFTR), have been shown to act as a buffering system by modulating the pH during amelogenesis (5,6).…”

“…As previously reported by us and others, ameloblasts play a critical role in regulating pH through various mechanisms, including the buffering system of amelogenin (AMLX) protein (3) and differential ion channel expression in differentiated ameloblasts (5,6). The ion channels, such as anion exchanger 2 (AE2), electrogenic bicarbonate cotransporter 1 (NBCe1), and cystic fibrosis (CF) conductance transmembrane regulator (CFTR), have been shown to act as a buffering system by modulating the pH during amelogenesis (5,6). During crystal mineralization, ameloblasts appear as a polarized layer of cells analogous to other bicarbonate-transporting (secretory) epithelia.…”

“…Therefore, an effective mechanism that can buffer protons for pH regulation is crucial for enamel mineralization (1). Ameloblasts have been proposed to play an important role in pH modulation during enamel formation by buffering amelogenin protein (3) and differential ion transporter expression during ameloblast differentiation (5,6).…”

“…Prediction tools indicated that the target genes of miR-224 include genes encoding a set of crucial ion transporters required for the development of normal enamel, including SLC4A4 and CFTR (5,6,41). NBCe1 (encoded by SLC4A4), AE2 (encoded by SLC4A2), and CFTR (encoded by CFTR) have been proposed to compose a buffering system during ameloblast differentiation and enamel mineralization (5,6).…”

“…During crystal mineralization, ameloblasts appear as a polarized layer of cells analogous to other bicarbonate-transporting (secretory) epithelia. AE2, encoded by SLC4A2, resides at the apical membrane, whereas NBCe1, encoded by SLC4A4, resides at the basolateral membrane (5,6). CFTR, a cyclic-AMP-regulated chloride channel, is located in the apical membranes of polarized ameloblasts.…”