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Matrix recruitment and calcium sequestration for spatial specific otoconia development.

Yang H, Zhao X, Xu Y, Wang L, He Q, Lundberg YW - PLoS ONE (2011)

Bottom Line: In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the mice leads to drastically reduced matrix-Ca(2+).Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins.Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.

View Article: PubMed Central - PubMed

Affiliation: Vestibular Neurogenetics Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America.

ABSTRACT
Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.

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Related in: MedlinePlus

Oc90 sequesters Ca2+ in vivo.Oc90 wt/ ratios of matrix-Ca2+ content in E17.5 and 7 week-old mice as measured with a cell impermeant fura-2 calibration kit (n = 8–16 in each tissue, age and genotype group). *** indicates p<0.001 between measurements of the utricle+saccule vs. cochlea.
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pone-0020498-g004: Oc90 sequesters Ca2+ in vivo.Oc90 wt/ ratios of matrix-Ca2+ content in E17.5 and 7 week-old mice as measured with a cell impermeant fura-2 calibration kit (n = 8–16 in each tissue, age and genotype group). *** indicates p<0.001 between measurements of the utricle+saccule vs. cochlea.

Mentions: By applying the fura-2 calibration kit, we indeed detected the trend hypothesized above (Figure 4). In the figure, the Oc90 wt/ ratios were obtained by using the averaged [Ca2+] values (based on the in vitro solution volume of 50 µl) from each tissue, genotype and age group (n = 8–16 in each group). Oc90 wt/ ratios of matrix-Ca2+ content in E17.5- and 7-week-old mice were consistently 8–9 in the macular matrix, but there was no significant difference between the two genotypes in the cochlear matrix where both genotypes produced low measurements. A preliminary test of wt and canals (including the ampulla ends) showed an outcome similar to that of the cochlea (data not shown). Maintenance of the macular matrix-Ca2+ content at the onset of murine adulthood, a stage considerably beyond the postnatal otoconia growth period (growth arrests at around P7), suggests a requirement for maintenance or possible potential for regeneration/neogenesis. Regardless of the gene expression levels after early postnatal stages, the matrix proteins are still present or even abundant (i.e. Oc90) [10] likely due to their stability.


Matrix recruitment and calcium sequestration for spatial specific otoconia development.

Yang H, Zhao X, Xu Y, Wang L, He Q, Lundberg YW - PLoS ONE (2011)

Oc90 sequesters Ca2+ in vivo.Oc90 wt/ ratios of matrix-Ca2+ content in E17.5 and 7 week-old mice as measured with a cell impermeant fura-2 calibration kit (n = 8–16 in each tissue, age and genotype group). *** indicates p<0.001 between measurements of the utricle+saccule vs. cochlea.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105080&req=5

pone-0020498-g004: Oc90 sequesters Ca2+ in vivo.Oc90 wt/ ratios of matrix-Ca2+ content in E17.5 and 7 week-old mice as measured with a cell impermeant fura-2 calibration kit (n = 8–16 in each tissue, age and genotype group). *** indicates p<0.001 between measurements of the utricle+saccule vs. cochlea.
Mentions: By applying the fura-2 calibration kit, we indeed detected the trend hypothesized above (Figure 4). In the figure, the Oc90 wt/ ratios were obtained by using the averaged [Ca2+] values (based on the in vitro solution volume of 50 µl) from each tissue, genotype and age group (n = 8–16 in each group). Oc90 wt/ ratios of matrix-Ca2+ content in E17.5- and 7-week-old mice were consistently 8–9 in the macular matrix, but there was no significant difference between the two genotypes in the cochlear matrix where both genotypes produced low measurements. A preliminary test of wt and canals (including the ampulla ends) showed an outcome similar to that of the cochlea (data not shown). Maintenance of the macular matrix-Ca2+ content at the onset of murine adulthood, a stage considerably beyond the postnatal otoconia growth period (growth arrests at around P7), suggests a requirement for maintenance or possible potential for regeneration/neogenesis. Regardless of the gene expression levels after early postnatal stages, the matrix proteins are still present or even abundant (i.e. Oc90) [10] likely due to their stability.

Bottom Line: In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the mice leads to drastically reduced matrix-Ca(2+).Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins.Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.

View Article: PubMed Central - PubMed

Affiliation: Vestibular Neurogenetics Laboratory, Boys Town National Research Hospital, Omaha, Nebraska, United States of America.

ABSTRACT
Otoconia are bio-crystals anchored to the macular sensory epithelium of the utricle and saccule in the inner ear for motion sensing and bodily balance. Otoconia dislocation, degeneration and ectopic calcification can have detrimental effects on balance and vertigo/dizziness, yet the mechanism underlying otoconia formation is not fully understood. In this study, we show that selected matrix components are recruited to form the crystal matrix and sequester Ca(2+) for spatial specific formation of otoconia. Specifically, otoconin-90 (Oc90) binds otolin through both domains (TH and C1q) of otolin, but full-length otolin shows the strongest interaction. These proteins have much higher expression levels in the utricle and saccule than other inner ear epithelial tissues in mice. In vivo, the presence of Oc90 in wildtype (wt) mice leads to an enrichment of Ca(2+) in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the mice leads to drastically reduced matrix-Ca(2+). In vitro, either Oc90 or otolin can increase the propensity of extracellular matrix to calcify in cell culture, and co-expression has a synergistic effect on calcification. Molecular modeling and sequence analysis predict structural features that may underlie the interaction and Ca(2+)-sequestering ability of these proteins. Together, the data provide a mechanism for the otoconial matrix assembly and the role of this matrix in accumulating micro-environmental Ca(2+) for efficient CaCO(3) crystallization, thus uncover a critical process governing spatial specific otoconia formation.

Show MeSH
Related in: MedlinePlus