New Perspectives on Amelotin and Amelogenesis

Abstract

This issue reports the first enamel malformations in amelotin (Amtn)-ablated mice (Nakayama et al. 2015). Among the proteins necessary for enamel formation, amelotin is one of the more recently discovered. It was discovered independently by 2 different laboratories (Iwasaki et al. 2005; Moffatt et al. 2006). The amelotin protein is enriched in proline, leucine, glutamine, and threonine (52% of total) and contains a perfectly conserved protein kinase CK2 phosphorylation site. Amelotin is a member of the secretory calcium-binding phosphoprotein (SCPP) family of proteins that evolved in vertebrates by gene duplication from a single ancestral gene (Kawasaki and Weiss 2003). Subsequent reiterative tandem gene duplication created 2 classes of genes, acidic SCPPs and proline/glutamine-rich SCPPs (Kawasaki et al. 2009). The SCPP genes encode secreted proteins with an SXE motif for phosphorylation by Golgi Casein Kinase (encoded by FAM20C) (Tagliabracci et al. 2012). In humans, there are 5 acidic and 18 P/Q-rich SCPP genes, which encode many of the secreted proteins that play prominent roles in enamel or dentin formation, such as amelogenin (AMELX), enamelin (ENAM), ameloblastin (AMBN), amelotin, odontogenic ameloblast-associated (ODAM), secretory calcium-binding phosphoprotein-proline-glutamine-rich 1 (SCPPPQ1), dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP). AMTN, ODAM, and SCPPPQ1 are expressed during the maturation stage of enamel development, when protein is removed from the fully thick enamel as it becomes the hardest substance in the body. The proteins encoded by these genes localize together within the basement membrane of maturation-stage ameloblasts and mediate the attachment of these epithelial cells to the mineralized tooth surface (Moffatt et al. 2014). Specifically, it was demonstrated that amelotin expression begins at the transition stage of enamel development and continues to be expressed throughout the maturation stage and into the reduced stage prior to when the incisor erupts (Somogyi-Ganss et al. 2012). Interestingly, Northern blots showed that amelotin was also expressed at low levels in the rat lung, and RT-PCR analysis showed it to be expressed at low levels in the mouse thymus, but not the lung (Moffatt et al. 2006). The detected low-level Amtn expression in the rat lung and mouse thymus are not likely biologically significant, since the EST databases show no amelotin transcripts from the lung in mice or humans and just 2 amelotin transcripts out of over 100,000 characterized from the mouse thymus, while human amelotin thymus transcripts are nonexistent.