Loss of biological control of enamel mineralization in amelogenin-phosphorylation-deficient mice

Stifler, Cayla A.; Yamazaki, Hajime; Gilbert, Pupa U.P.A.; Margolis, Henry C.; Beniash, Elia

doi:10.1016/j.jsb.2022.107844

Loss of biological control of enamel mineralization in amelogenin-phosphorylation-deficient mice

Journal Article · Fri Feb 25 00:00:00 EST 2022 · Journal of Structural Biology

DOI:https://doi.org/10.1016/j.jsb.2022.107844· OSTI ID:1963451

Stifler, Cayla A. ^[1]; Yamazaki, Hajime ^[2]; Gilbert, Pupa U.P.A. ^[3]; Margolis, Henry C. ^[2]; Beniash, Elia ^[2]

Univ. of Wisconsin, Madison, WI (United States)
Univ. of Pittsburgh, PA (United States)
Univ. of Wisconsin, Madison, WI (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Amelogenin, the most abundant enamel matrix protein, plays several critical roles in enamel formation. Importantly, we previously found that the singular phosphorylation site at Ser16 in amelogenin plays an essential role in amelogenesis. Studies of genetically knock-in (KI) modified mice in which Ser16 in amelogenin is substituted with Ala that prevents amelogenin phosphorylation, and in vitro mineralization experiments, have shown that phosphorylated amelogenin transiently stabilizes amorphous calcium phosphate (ACP), the initial mineral phase in forming enamel. Furthermore, KI mice exhibit dramatic differences in the enamel structure compared with wild type (WT) mice, including thinner enamel lacking enamel rods and ectopic surface calcifications. Here, we now demonstrate that amelogenin phosphorylation also affects the organization and composition of mature enamel mineral. In this work, we compared WT, KI, and heterozygous (HET) enamel and found that in the WT elongated crystals are co-oriented within each rod, however, their c-axes are not aligned with the rods' axes. In contrast, in rod-less KI enamel, crystalline c-axes are less co-oriented, with misorientation progressively increasing toward the enamel surface, which contains spherulites, with a morphology consistent with abiotic formation. Furthermore, we found significant differences in enamel hardness and carbonate content between the genotypes. ACP was also observed in the interrod of WT and HET enamel, and throughout aprismatic KI enamel. In conclusion, amelogenin phosphorylation plays crucial roles in controlling structural, crystallographic, mechanical, and compositional characteristics of dental enamel. Thus, loss of amelogenin phosphorylation leads to a reduction in the biological control over the enamel mineralization process.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR); National Science Foundation (NSF); USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division

Grant/Contract Number:: AC02-05CH11231; FG02-07ER15899

OSTI ID:: 1963451

Journal Information:: Journal of Structural Biology, Journal Name: Journal of Structural Biology Journal Issue: 2 Vol. 214; ISSN 1047-8477

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (60)

Built to last: The structure, function, and evolution of primate dental enamel Maas, Mary Carol; Dumont, Elizabeth R. Evolutionary Anthropology: Issues, News, and Reviews, Vol. 8, Issue 4 https://doi.org/10.1002/(SICI)1520-6505(1999)8:4<133::AID-EVAN4>3.0.CO;2-F	journal	January 1999
The molecular etiologies and associated phenotypes of amelogenesis imperfecta Wright, J. Timothy American Journal of Medical Genetics Part A, Vol. 140A, Issue 23 https://doi.org/10.1002/ajmg.a.31358	journal	January 2006
A three-dimensional reconstruction of the rods in rat maxillary incisor enamel Warshawsky, H.; Smith, C. E. The Anatomical Record, Vol. 169, Issue 3 https://doi.org/10.1002/ar.1091690308	journal	March 1971
Enamel ribbons, surface nodules, and octacalcium phosphate in C57 BL /6 Amelx ^−/− mice and Amelx ^+/− lyonization Hu, Yuanyuan; Smith, Charles E.; Cai, Zhonghou Molecular Genetics & Genomic Medicine, Vol. 4, Issue 6 https://doi.org/10.1002/mgg3.252	journal	October 2016
Solidification of eutectic Ni-Ni3Ti alloys Geveling, N. N.; Maslenkov, S. B. Metal Science and Heat Treatment, Vol. 18, Issue 9 https://doi.org/10.1007/BF00704110	journal	September 1976
Carbonate Assignment and Calibration in the Raman Spectrum of Apatite Awonusi, Ayorinde; Morris, Michael D.; Tecklenburg, Mary M. J. Calcified Tissue International, Vol. 81, Issue 1 https://doi.org/10.1007/s00223-007-9034-0	journal	June 2007
Bicarbonate Transport During Enamel Maturation Yin, Kaifeng; Paine, Michael L. Calcified Tissue International, Vol. 101, Issue 5 https://doi.org/10.1007/s00223-017-0311-2	journal	August 2017
MicroRaman Spectral Study of the PO 4 and CO 3 Vibrational Modes in Synthetic and Biological Apatites Penel, G.; Leroy, G.; Rey, C. Calcified Tissue International, Vol. 63, Issue 6 https://doi.org/10.1007/s002239900561	journal	December 1998
Mary Lyon and the hypothesis of random X chromosome inactivation Harper, Peter S. Human Genetics, Vol. 130, Issue 2 https://doi.org/10.1007/s00439-011-1013-x	journal	June 2011
The distribution of carbonate in enamel and its correlation with structure and mechanical properties Xu, Changqi; Reed, Rachel; Gorski, Jeffrey P. Journal of Materials Science, Vol. 47, Issue 23 https://doi.org/10.1007/s10853-012-6693-7	journal	July 2012
X-linked (recessive) hypomaturation amelogenesis imperfecta: A prosthodontic, genetic, and histopathologic report Patel, Raj-Rajendra A.; Hovijitra, Suteera; Kafrawy, Abdel H. The Journal of Prosthetic Dentistry, Vol. 66, Issue 3 https://doi.org/10.1016/0022-3913(91)90270-7	journal	September 1991
Amelogenesis imperfecta phenotype–genotype correlations with two amelogenin gene mutations Hart, P. S.; Aldred, M. J.; Crawford, P. J. M. Archives of Oral Biology, Vol. 47, Issue 4 https://doi.org/10.1016/S0003-9969(02)00003-1	journal	April 2002
Organization of oscillatory zoning in zircon: analysis, scaling, geochemistry, and model of a zircon from Kipawa, Quebec, Canada Fowler, Anthony; Prokoph, Andreas; Stern, Richard Geochimica et Cosmochimica Acta, Vol. 66, Issue 2 https://doi.org/10.1016/S0016-7037(01)00774-8	journal	January 2002
Continuous synthesis of amorphous carbonated apatites Tadic, D.; Peters, F.; Epple, M. Biomaterials, Vol. 23, Issue 12 https://doi.org/10.1016/S0142-9612(01)00390-8	journal	June 2002
Compensation of charging in X-PEEM: a successful test on mineral inclusions in 4.4Ga old zircon De Stasio, Gelsomina; Frazer, Bradley H.; Gilbert, Benjamin Ultramicroscopy, Vol. 98, Issue 1 https://doi.org/10.1016/S0304-3991(03)00088-3	journal	December 2003
Charging phenomena in PEEM imaging and spectroscopy Gilbert, B.; Andres, R.; Perfetti, P. Ultramicroscopy, Vol. 83, Issue 1-2 https://doi.org/10.1016/S0304-3991(99)00196-5	journal	May 2000
Nature’s design solutions in dental enamel: Uniting high strength and extreme damage resistance Wilmers, Jana; Bargmann, Swantje Acta Biomaterialia, Vol. 107 https://doi.org/10.1016/j.actbio.2020.02.019	journal	April 2020
A survey of carbonic anhydrase mRNA expression in enamel cells Lacruz, Rodrigo S.; Hilvo, Mika; Kurtz, Ira Biochemical and Biophysical Research Communications, Vol. 393, Issue 4 https://doi.org/10.1016/j.bbrc.2010.02.116	journal	March 2010
On the R-curve behavior of human tooth enamel Bajaj, Devendra; Arola, Dwayne D. Biomaterials, Vol. 30, Issue 23-24 https://doi.org/10.1016/j.biomaterials.2009.04.017	journal	August 2009
Cytoskeleton, intercellular junctions, planar cell polarity, and cell movement in amelogenesis Nishikawa, Sumio Journal of Oral Biosciences, Vol. 59, Issue 4 https://doi.org/10.1016/j.job.2017.07.002	journal	November 2017
The effect of recombinant mouse amelogenins on the formation and organization of hydroxyapatite crystals in vitro Beniash, Elia; Simmer, James P.; Margolis, Henry C. Journal of Structural Biology, Vol. 149, Issue 2 https://doi.org/10.1016/j.jsb.2004.11.001	journal	February 2005
Otolith crystals (in Carapidae): Growth and habit Parmentier, Eric; Cloots, Rudi; Warin, Roger Journal of Structural Biology, Vol. 159, Issue 3 https://doi.org/10.1016/j.jsb.2007.05.006	journal	September 2007
pH triggered self-assembly of native and recombinant amelogenins under physiological pH and temperature in vitro Wiedemann-Bidlack, Felicitas B.; Beniash, Elia; Yamakoshi, Yasuo Journal of Structural Biology, Vol. 160, Issue 1 https://doi.org/10.1016/j.jsb.2007.06.007	journal	October 2007
Transient amorphous calcium phosphate in forming enamel Beniash, Elia; Metzler, Rebecca A.; Lam, Raymond S. K. Journal of Structural Biology, Vol. 166, Issue 2 https://doi.org/10.1016/j.jsb.2009.02.001	journal	May 2009
Effects of phosphorylation on the self-assembly of native full-length porcine amelogenin and its regulation of calcium phosphate formation in vitro Wiedemann-Bidlack, Felicitas B.; Kwak, Seo-Young; Beniash, Elia Journal of Structural Biology, Vol. 173, Issue 2 https://doi.org/10.1016/j.jsb.2010.11.006	journal	February 2011
Possible role of DMP1 in dentin mineralization Beniash, Elia; Deshpande, Atul S.; Fang, Ping An Journal of Structural Biology, Vol. 174, Issue 1 https://doi.org/10.1016/j.jsb.2010.11.013	journal	April 2011
Crystal lattice tilting in prismatic calcite Olson, Ian C.; Metzler, Rebecca A.; Tamura, Nobumichi Journal of Structural Biology, Vol. 183, Issue 2 https://doi.org/10.1016/j.jsb.2013.06.006	journal	August 2013
Spectromicroscope for the PHotoelectron Imaging of Nanostructures with X-rays (SPHINX): performance in biology, medicine and geology Frazer, Bradley H.; Girasole, Marco; Wiese, Lisa M. Ultramicroscopy, Vol. 99, Issue 2-3 https://doi.org/10.1016/j.ultramic.2003.10.001	journal	May 2004
Control of Calcium Phosphate Nucleation and Transformation through Interactions of Enamelin and Amelogenin Exhibits the “Goldilocks Effect” Tao, Jinhui; Fijneman, Andreas; Wan, Jiaqi Crystal Growth & Design, Vol. 18, Issue 12 https://doi.org/10.1021/acs.cgd.8b01066	journal	October 2018
Spherulitic Growth of Coral Skeletons and Synthetic Aragonite: Nature’s Three-Dimensional Printing Sun, Chang-Yu; Marcus, Matthew A.; Frazier, Matthew J. ACS Nano, Vol. 11, Issue 7 https://doi.org/10.1021/acsnano.7b00127	journal	June 2017
The Tooth Enamel Protein, Porcine Amelogenin, Is an Intrinsically Disordered Protein with an Extended Molecular Configuration in the Monomeric Form ^† Delak, Katya; Harcup, Craig; Lakshminarayanan, Rajamani Biochemistry, Vol. 48, Issue 10 https://doi.org/10.1021/bi802175a	journal	March 2009
Mechanism of Calcium Oxalate Monohydrate Kidney Stones Formation: Layered Spherulitic Growth Al-Atar, Usama; Bokov, Alexei A.; Marshall, Dan Chemistry of Materials, Vol. 22, Issue 4 https://doi.org/10.1021/cm901751g	journal	February 2010
Phosphorylated Proteins and Control over Apatite Nucleation, Crystal Growth, and Inhibition George, Anne; Veis, Arthur Chemical Reviews, Vol. 108, Issue 11 https://doi.org/10.1021/cr0782729	journal	October 2008
Faster Crystallization during Coral Skeleton Formation Correlates with Resilience to Ocean Acidification Schmidt, Connor A.; Stifler, Cayla A.; Luffey, Emily L. Journal of the American Chemical Society, Vol. 144, Issue 3 https://doi.org/10.1021/jacs.1c11434	journal	January 2022
X-ray Linear Dichroism in Apatite Stifler, Cayla A.; Wittig, Nina Kølln; Sassi, Michel Journal of the American Chemical Society, Vol. 140, Issue 37 https://doi.org/10.1021/jacs.8b05547	journal	September 2018
Oxygen Spectroscopy and Polarization-Dependent Imaging Contrast (PIC)-Mapping of Calcium Carbonate Minerals and Biominerals DeVol, Ross T.; Metzler, Rebecca A.; Kabalah-Amitai, Lee The Journal of Physical Chemistry B, Vol. 118, Issue 28 https://doi.org/10.1021/jp503700g	journal	May 2014
Gene Action in the X-chromosome of the Mouse (Mus musculus L.) Lyon, Mary F. Nature, Vol. 190, Issue 4773 https://doi.org/10.1038/190372a0	journal	April 1961
The hidden structure of human enamel Beniash, Elia; Stifler, Cayla A.; Sun, Chang-Yu Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12185-7	journal	September 2019
MEPHISTO: Performance tests of a novel synchrotron imaging photoelectron spectromicroscope De Stasio, Gelsomina; Capozi, M.; Lorusso, G. F. Review of Scientific Instruments, Vol. 69, Issue 5 https://doi.org/10.1063/1.1148899	journal	May 1998
Remarkable resilience of teeth Chai, H.; Lee, J. J. -W.; Constantino, P. J. Proceedings of the National Academy of Sciences, Vol. 106, Issue 18 https://doi.org/10.1073/pnas.0902466106	journal	April 2009
Intrinsically disordered proteins drive enamel formation via an evolutionarily conserved self-assembly motif Wald, Tomas; Spoutil, Frantisek; Osickova, Adriana Proceedings of the National Academy of Sciences, Vol. 114, Issue 9 https://doi.org/10.1073/pnas.1615334114	journal	February 2017
The energetic basis for hydroxyapatite mineralization by amelogenin variants provides insights into the origin of amelogenesis imperfecta Tao, Jinhui; Shin, Yongsoon; Jayasinha, Rajith Proceedings of the National Academy of Sciences, Vol. 116, Issue 28 https://doi.org/10.1073/pnas.1815654116	journal	June 2019
Amelogenin-deficient Mice Display an Amelogenesis Imperfecta Phenotype Gibson, Carolyn W.; Yuan, Zhi-An; Hall, Bradford Journal of Biological Chemistry, Vol. 276, Issue 34 https://doi.org/10.1074/jbc.M104624200	journal	June 2001
Role of 20-kDa Amelogenin (P148) Phosphorylation in Calcium Phosphate Formation in Vitro Kwak, Seo-Young; Wiedemann-Bidlack, Felicitas B.; Beniash, Elia Journal of Biological Chemistry, Vol. 284, Issue 28 https://doi.org/10.1074/jbc.M109.020370	journal	May 2009
Amelogenin phosphorylation regulates tooth enamel formation by stabilizing a transient amorphous mineral precursor Shin, Nah-Young; Yamazaki, Hajime; Beniash, Elia Journal of Biological Chemistry, Vol. 295, Issue 7 https://doi.org/10.1074/jbc.RA119.010506	journal	February 2020
How the tooth got its stripes: patterning via strain-cued motility Cox, Brian N. Journal of The Royal Society Interface, Vol. 10, Issue 84 https://doi.org/10.1098/rsif.2013.0266	journal	July 2013
Polarization-dependent imaging contrast in abalone shells Metzler, Rebecca A.; Zhou, Dong; Abrecht, Mike Physical Review B, Vol. 77, Issue 6 https://doi.org/10.1103/PhysRevB.77.064110	journal	February 2008
Effect of phosphorylation on the interaction of calcium with leucine-rich amelogenin peptide: Effect of phosphorylation on LRAP conformation Le Norcy, Elvire; Kwak, Seo-Young; Allaire, Marc European Journal of Oral Sciences, Vol. 119 https://doi.org/10.1111/j.1600-0722.2011.00900.x	journal	December 2011
Amorphous intergranular phases control the properties of rodent tooth enamel Gordon, L. M.; Cohen, M. J.; MacRenaris, K. W. Science, Vol. 347, Issue 6223 https://doi.org/10.1126/science.1258950	journal	February 2015
The contribution of XANES spectroscopy to tribology Nicholls, M.; Najman, M. N.; Zhang, Z. Canadian Journal of Chemistry, Vol. 85, Issue 10 https://doi.org/10.1139/v07-093	journal	October 2007
The Amelogenin C-Terminus Is Required for Enamel Development Pugach, M. K.; Li, Y.; Suggs, C. Journal of Dental Research, Vol. 89, Issue 2 https://doi.org/10.1177/0022034509358392	journal	December 2009
Structural Changes in Amelogenin upon Self-assembly and Mineral Interactions Beniash, E.; Simmer, J. P.; Margolis, H. C. Journal of Dental Research, Vol. 91, Issue 10 https://doi.org/10.1177/0022034512457371	journal	August 2012
Variations in the Chemical Composition of Human Enamel Weatherell, J. A.; Robinson, C.; Hallsworth, A. S. Journal of Dental Research, Vol. 53, Issue 2 https://doi.org/10.1177/00220345740530020501	journal	March 1974
Comparative Immunochemical Analyses of the Developmental Expression and Distribution of Ameloblastin and Amelogenin in Rat Incisors Nanci, A.; Zalzal, S.; Lavoie, P. Journal of Histochemistry & Cytochemistry, Vol. 46, Issue 8 https://doi.org/10.1177/002215549804600806	journal	August 1998
Developmental Changes in the PH of Enamel Fluid and Its Effects On Matrix-Resident Proteinases Smith, C. E.; Issid, M.; Margolis, H. C. Advances in Dental Research, Vol. 10, Issue 2 https://doi.org/10.1177/08959374960100020701	journal	November 1996
Role of Macromolecular Assembly of Enamel Matrix Proteins in Enamel Formation Margolis, H. C.; Beniash, E.; Fowler, C. E. Journal of Dental Research, Vol. 85, Issue 9 https://doi.org/10.1177/154405910608500902	journal	September 2006
Compositional Determinants of Mechanical Properties of Enamel Baldassarri, M.; Margolis, H. C.; Beniash, E. Journal of Dental Research, Vol. 87, Issue 7 https://doi.org/10.1177/154405910808700711	journal	July 2008
Spherulitic rhyolites of the Archean Blake River Group, Canada; implications for stratigraphic correlation and volcanogenic massive sulfide exploration Peloquin, A. S.; Verpaelst, P.; Ludden, J. N. Economic Geology, Vol. 91, Issue 2 https://doi.org/10.2113/gsecongeo.91.2.343	journal	April 1996
The eggshell: structure, composition and mineralization Hincke, Maxwell, T. Frontiers in Bioscience, Vol. 17, Issue 1 https://doi.org/10.2741/3985	journal	January 2012
Amelogenesis Imperfecta; Genes, Proteins, and Pathways Smith, Claire E. L.; Poulter, James A.; Antanaviciute, Agne Frontiers in Physiology, Vol. 8 https://doi.org/10.3389/fphys.2017.00435	journal	June 2017

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59 BASIC BIOLOGICAL SCIENCES
Amelogenin
Biomineralization
Dental enamel
Phosphorylation

Loss of biological control of enamel mineralization in amelogenin-phosphorylation-deficient mice

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