Proteins in Enamel Development: Secretome, Transport and Posttranslational Fate
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Amelogenesis is a process involving formation of mineralized tooth enamel by ameloblast cells. During amelogenesis, ameloblasts secrete matrix consisting of enamel proteins that facilitate future enamel prism formation. In this study, we focused on understanding the transportation and fate of enamel proteins from the time of secretion in the enamel matrix to the stage where the fragments come in contact with the initial enamel prisms and thereafter. For the first part, we used focused on the transportation part of proteins using Phospho1 knockout mice to understand the role of secretory vesicles in ameloblasts and the transportation of proteins through ameloblasts. Our study demonstrated the presence of PHOSPHO1 protein in ameloblasts including the enamel layer and the ameloblast Tomes’ processes. The effect of disruption of the vesicular coat protein in Phospho1 -/- mice significantly affected physiological enamel mineralization. A loss of enamel prism organization was observed and a 25% increase in enamel layer was noted indicating the retention of enamel proteins in the matrix due to transportation failure. Phospho1 -/- mice indicated that the matrix vesicular protein PHOSPHO 1 is an integral part of enamel mineralization process. For the second part, our intent was to use a mouse molar model to establish a temporo-spatial correlation of the events occurring through the different stages of enamel development and document the consequential changes in the enamel matrix proteins. Our proteomic analysis identified some novel proteins which may also play a key role during amelogenesis. The final part of the study focuses on amelogenin and its fate once it is secreted in the matrix. Our data demonstrates that the protein matrix configuration changes substantially from the time it is transported through the ameloblasts and the amelogenin fragmentation plays a major role in enamel crystal growth. The Western blot analysis of enamel matrix from different layers of porcine enamel tooth organ documented the close association of amelogenin C-terminus with the apatite crystal surface while the N-terminus fragments are likely retained in between the growing enamel crystals indicating perhaps the C-terminal fragments help with prism growth in C-axis direction while N-terminal fragments maintain the interprismatic distance.
Pandya, Mirali Gaurang (2019). Proteins in Enamel Development: Secretome, Transport and Posttranslational Fate. Doctoral dissertation, Texas A&M University. Available electronically from