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.
Highlights
Biomineralization is an important biological process that provides structural support and a mineral depot to a broad array of living organisms from mollusks to humans
We demonstrate that recombinant histidine tagged mouse Otoconin-90 modulates calcite crystal morphology and growth kinetics when added to CaCO3 crystal growth solution and this effect is potentiated by co-administration with rhOtolin-1
Our preliminary His-tag pull down analysis in addition to the data presented by Deans et al (2010) has shown clear evidence of an interaction between Flag tagged recombinant mouse Otolin-1 and recombinant mouse Otoconin 90 (OC90)-His, suggesting that proteinprotein interaction could represent the molecular mechanism corresponding to the observed recruitment of recombinant histidine tagged mouse Otoconin-90 (rmOC90) by rmOtolin-1
Summary
Biomineralization is an important biological process that provides structural support and a mineral depot to a broad array of living organisms from mollusks to humans. Understanding the critical molecular interactions of the players at the organic and inorganic interface will help answer many fundamental questions regarding processes in the formation of crystallites or mineralized fibrils that are common in biological tissues such as vertebrate bone, tooth dentin [1], and otoconia. Advancing age accentuates demineralization which progresses to degeneration and fragmentation of otoconia [5]. This leads to loss of equilibrium and a propensity to falling which may result in bone fracture or death. Social isolation and cognitive decline are consequences stemming from this pathology These outcomes constitute a major socioeconomic burden which is becoming more pronounced with the increasing longevity of the human population. BPV is most prevalent between the ages of 60 and 80, in postmenopausal women suffering from osteoporosis [9,10]
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