The long-term goal of this proposed work is to characterize protein-protein interactions involving the enamel extracellular matrix proteins, as well as proteins integral to the plasma membrane of ameloblast cells, and characterize how these interactions regulate enamel formation. To achieve this the molecular biochemistry of biglycan, Cd63, Anxa2 and Lampl, and their relationship to the major enamel matrix proteins, will be studied. The hypothesis of this grant application is """"""""protein-protein interactions involving secreted enamel matrix proteins and the secretory surface of ameloblast cells (Tomes'processes) play a key role in the formation of the enamelprismatic structure."""""""" To test this hypothesis we propose three specific aims. These are to: 1) define, using in situ hybridization and mouse-specific antibodies, the spatiotemporal expression patterns for Cd63, Anxa2 and Lampl within the murine developing incisor tooth, and relate these expression profiles to those of their respective ligand (enamel matrix protein partner), and the stages of enamel biomineralization;2) demonstrate that the protein-protein interactions previously identified for the enamel matrix proteins and biglycan, Cd63, Anxa2 and Lampl occur in vivo and have physiological significance, and to define the minimal binding domains of Cd63 and Lampl that enable their interaction with amelogenin;3) define and disrupt the receptor-mediated molecular mechanism that permits the enamel matrix expression levels of biglycan to influence or control amelogenin expression levels, and the subsequent events of enamel biomineralization. Knowledge gained from this and related studies may lead to better dental and non-dental materials, or biomimetics. This data will be critical to others in their pursuits to regenerate an entire tooth. For tooth regeneration to become a reality, the protein- protein interactions involving the key dental proteins must be known and understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013404-10
Application #
7795241
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Wan, Jason
Project Start
2000-03-01
Project End
2014-03-31
Budget Start
2010-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2010
Total Cost
$375,795
Indirect Cost
Name
University of Southern California
Department
Dentistry
Type
Schools of Dentistry
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Wen, Xin; Lacruz, Rodrigo S; Smith, Charles E et al. (2014) Gene-expression profile and localization of Na+/K(+)-ATPase in rat enamel organ cells. Eur J Oral Sci 122:21-6
Lacruz, R S; Smith, C E; Kurtz, I et al. (2013) New paradigms on the transport functions of maturation-stage ameloblasts. J Dent Res 92:122-9
Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin et al. (2013) Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis. J Bone Miner Res 28:672-87
Wen, Xin; Paine, Michael L (2013) Iron deposition and ferritin heavy chain (Fth) localization in rodent teeth. BMC Res Notes 6:1
Lees, James D; Robinson, Colin; Shore, Roger C et al. (2013) Cellular uptake and processing of enamel matrix derivative by human periodontal ligament fibroblasts. Arch Oral Biol 58:348-54
Lacruz, Rodrigo S; Smith, Charles E; Moffatt, Pierre et al. (2012) Requirements for ion and solute transport, and pH regulation during enamel maturation. J Cell Physiol 227:1776-85
Lacruz, Rodrigo S; Hacia, Joseph G; Bromage, Timothy G et al. (2012) The circadian clock modulates enamel development. J Biol Rhythms 27:237-45
Lacruz, Rodrigo S; Nakayama, Yohei; Holcroft, James et al. (2012) Targeted overexpression of amelotin disrupts the microstructure of dental enamel. PLoS One 7:e35200
Lacruz, Rodrigo S; Smith, Charles E; Bringas Jr, Pablo et al. (2012) Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling. J Cell Physiol 227:2264-75
Snead, Malcolm L; Zhu, Dan-Hong; Lei, Yaping et al. (2011) A simplified genetic design for mammalian enamel. Biomaterials 32:3151-7

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