Abundant AMEL proteins are responsible for generating proper enamel thickness and structure, and most of those proteins include a conserved hydrophilic C-terminus. Mice that express AMEL lacking the C-terminal show deficient enamel in the molar teeth, suggesting that AMEL, especially the C-terminus, is essential for proper enamel density, volume, and organization [15]. AMEL regulates the formation of these selleck chemicals crystalline arrays via cooperative interactions with the forming mineral phase. Cryoelectron

microscopy analysis has shown that AMEL undergoes stepwise hierarchical self-assembly. Furthermore, interactions between AMEL hydrophilic C-terminal telopeptides are essential for oligomer formation and subsequent steps ABT-263 research buy of hierarchical self-assembly. The pre-nucleation clusters subsequently fuse together to form needle-shaped mineral particles, leading to the formation of bundles of crystallites, the hallmark structural organization of enamel forming at a nanoscale size [16]. AMEL is soluble at a low pH and self-assembles to form higher order structures at physiological pH. In FTIR spectroscopy (FTIRS) studies of the pH-triggered assembly of recombinant

porcine AMEL performed to elucidate the mechanisms of its assembly and interactions with calcium phosphate mineral, AMEL at a pH of 3.0 is found to exist in an unfolded disordered state, while increases in pH lead to structural ordering, manifested by increases in intra- and intermolecular beta-sheet structures and decreases in random coil and beta-turns. AMEL assembled at a pH of 7.2 is also found to contain large portions of extended intramolecular beta-sheet structures, and interactions with minerals lead to a reduction in protein structural organization. These findings indicate that AMEL has an intrinsic structural flexibility to accommodate

interactions with both forming and mature calcium phosphate mineral phases and provide new insights into the potential importance of AMEL–mineral interactions in enamel biomineralization [17]. Recent studies have also revealed that AMEL has cell signaling properties. Although the AMEL protein has been described as a specific product Carbachol of ameloblasts, recent findings have shown that AMEL is expressed in bone marrow stromal cells. Researchers have also demonstrated that the full-length AMEL protein interacts with LAMP1, an AMEL receptor, and increases the proliferation of mesenchymal stem cells through the MAPK-ERK signaling pathway [18]. One of the AMEL splicing isoforms, leucine-rich amelogenin peptide (LRAP), induces osteogenesis in osteoprogenitor cells. LPAP activates the canonical Wnt signaling pathway to induce the osteogenic differentiation of mouse ES cells through the concerted regulation of Wnt agonists and antagonists.