Matrix recruitment and calcium sequestration for spatial specific Otoconia development

Hua Yang, Xing Zhao, Yinfang Xu, Lili Wang, Quanyuan He, Yunxia W Lundberg

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 Ca2+ 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 Ca2+ in the luminal matrices of the utricle and saccule, whereas absence of Oc90 in the null mice leads to drastically reduced matrix-Ca2+. 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 Ca2+-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 Ca2+ for efficient CaCO3 crystallization, thus uncover a critical process governing spatial specific otoconia formation.

Original languageEnglish (US)
Article numbere20498
JournalPloS one
Volume6
Issue number5
DOIs
StatePublished - Jun 6 2011

Fingerprint

Otolithic Membrane
otoliths
Saccule and Utricle
Calcium
calcium
Crystals
Molecular modeling
Crystallization
Cell culture
Structural analysis
calcification
Inner Ear
Proteins
crystals
Tissue
ears
mice
epithelium
Epithelium
Vertigo

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Matrix recruitment and calcium sequestration for spatial specific Otoconia development. / Yang, Hua; Zhao, Xing; Xu, Yinfang; Wang, Lili; He, Quanyuan; Lundberg, Yunxia W.

In: PloS one, Vol. 6, No. 5, e20498, 06.06.2011.

Research output: Contribution to journalArticle

Yang, Hua ; Zhao, Xing ; Xu, Yinfang ; Wang, Lili ; He, Quanyuan ; Lundberg, Yunxia W. / Matrix recruitment and calcium sequestration for spatial specific Otoconia development. In: PloS one. 2011 ; Vol. 6, No. 5.
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