Ameloblastin and its multifunctionality in amelogenesis: A review

• Published in: Matrix biology 2024-08, Vol.131, p.62-76
• Main Authors: Kegulian, Natalie C., Visakan, Gayathri, Bapat, Rucha Arun, Moradian-Oldak, Janet
• Format: Article
• Language: English
• Subjects: Ameloblastin; Ameloblasts; Amelogenesis; Amphipathic helix; Enamel; Matricellular proteins; Protein multifunctionality
• ISSN: 0945-053X; 1569-1802; 1569-1802
• DOI: 10.1016/j.matbio.2024.05.007

•Ameloblastin (Ambn) is multifunctional in its facilitation of enamel formation.•Human amelogenesis imperfecta cases and animal models emphasize importance of Ambn.•Its functions include ameloblast cell signaling, polarization, and matrix adhesion.•A conserved amphipathic helix motif mediates direct Ambn-cell membrane interaction.•The motif is part of a multitargeting domain mediating multiple Ambn interactions.•These various interactions could enable Ambn's cell polarization and adhesion roles. Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro, and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization.