title: In vitro calcite crystal morphology is modulated by otoconial proteins otolin-1 and otoconin-90.
abstract: Otoconia are formed embryonically and are instrumental in detecting linear acceleration and gravity. Degeneration and fragmentation of otoconia in elderly patients leads to imbalance resulting in higher frequency of falls that are positively correlated with the incidence of bone fractures and death. In this work we investigate the roles otoconial proteins Otolin-1 and Otoconin 90 (OC90) perform in the formation of otoconia. We demonstrate by rotary shadowing and atomic force microscopy (AFM) experiments that Otolin-1 forms homomeric protein complexes and self-assembled networks supporting the hypothesis that Otolin-1 serves as a scaffold protein of otoconia. Our calcium carbonate crystal growth data demonstrate that Otolin-1 and OC90 modulate in vitro calcite crystal morphology but neither protein is sufficient to produce the shape of otoconia. Coadministration of these proteins produces synergistic effects on crystal morphology that contribute to morphology resembling otoconia.
authors.affiliation: Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: K Trent
authors.initials: KT
authors.lastname: Moreland
authors.affiliation: Department of Chemistry, The George Washington University, Washington, D.C., United States of America.
authors.forename: Mina
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Wenfu
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Rowley
authors.affiliation: Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
authors.affiliation: The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: De Yoreo
authors.affiliation: Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Ruediger
authors.initials: R
authors.lastname: Thalmann
mesh_terms: D001483:Base Sequence; D002119:Calcium Carbonate / Q000737:chemistry*; D002135:Calcium-Binding Proteins; D003460:Crystallization; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C116608:OC90 protein, human; C449659:otolin-1; D002119:Calcium Carbonate
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