Proteomics and genetics of dental enamel.
The initiation of enamel crystals at the dentino-enamel junction is associated with the expression of dentin sialophosphoprotein (DSPP, a gene normally linked with dentin formation), three 'structural' enamel proteins--amelogenin (AMELX), enamelin (ENAM), and ameloblastin (AMBN)--and a matrix metalloproteinase, enamelysin (MMP20). Enamel formation proceeds with the steady elongation of the enamel crystals at a mineralization front just beneath the ameloblast distal membrane, where these proteins are secreted. As the crystal ribbons lengthen, enamelysin processes the secreted proteins. Some of the cleavage products accumulate in the matrix, others are reabsorbed back into the ameloblast. Once crystal elongation is complete and the enamel layer reaches its final thickness, kallikrein 4 (KLK4) facilitates the breakdown and reabsorption of accumulated enamel matrix proteins. The importance of the extracellular matrix proteins to proper tooth development is best illustrated by the dramatic dental phenotypes observed in the targeted knockouts of enamel matrix genes in mice (Dspp, Amelx, Ambn, Mmp20) and in human kindreds with defined mutations in the genes (DSPP, AMELX, ENAM, MMP20, KLK4) encoding these matrix proteins. However, ablation studies alone cannot give specific mechanistic information on how enamel matrix proteins combine to catalyze the formation of enamel crystals. The best approach for determining the molecular mechanism of dental enamel formation is to reconstitute the matrix and synthesize enamel crystals in vitro. Here, we report refinements to the procedures used to isolate porcine enamel and dentin proteins, recent advances in the characterization of enamel matrix protein posttranslational modifications, and summarize the results of human genetic studies that associate specific mutations in the genes encoding matrix proteins with a range of dental phenotypes.
Hu
Jan C-C
JC
University of Michigan Dental Research Lab, Ann Arbor, Mich. 48108, USA.
Yamakoshi
Yasuo
Y
Yamakoshi
Fumiko
F
Krebsbach
Paul H
PH
Simmer
James P
JP
D000566:Amelogenesis / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D003743:Dental Enamel / Q000254:growth & development* / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D040901:Proteomics; D034421:Sus scrofa
D003746:Dental Enamel Proteins