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Mammalian Otolin: A Multimeric Glycoprotein Specific to the Inner Ear that Interacts with Otoconial Matrix Protein Otoconin-90 and Cerebellin-1
PLOS ONE (2010)
  • Michael R. Dean, Johns Hopkins University School of Medicine
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine
  • G. William Wong, Johns Hopkins University School of Medicine
Abstract
Background

The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of the vestibular maculae to respond to linear accelerations and gravity. In teleosts, Otolin is required for the proper anchoring of otolith crystals to the sensory maculae. Otoconia detachment and subsequent entrapment in the semicircular canals can result in benign paroxysmal positional vertigo (BPPV), a common form of vertigo for which the molecular basis is unknown. Several cDNAs encoding protein components of the mammalian otoconia and otoconial membrane have recently been identified, and mutations in these genes result in abnormal otoconia formation and balance deficits.

Principal Findings

Here we describe the cloning and characterization of mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain that is homologous to the immune complement C1q, and contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order oligomeric complexes. The expression of otolin mRNA is restricted to the inner ear, and immunohistochemical analysis identified Otolin protein in support cells of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin forms protein complexes with Cerebellin-1 and Otoconin-90, two protein constituents of the otoconia, when expressed in vitro. Otolin was also found in subsets of support cells and non-sensory cells of the cochlea, suggesting that Otolin is also a component of the tectorial membrane.

Conclusion

Given the importance of Otolin in lower organisms, the molecular cloning and biochemical characterization of the mammalian Otolin protein may lead to a better understanding of otoconial development and vestibular dysfunction.


Keywords
  • inner ear,
  • otolith,
  • extracellular matrix,
  • complementary dna,
  • collagens,
  • glycoproteins,
  • mammalian otolin,
  • otoconial matrix protein,
  • otoconin-90,
  • cerebellin-1
Publication Date
September 15, 2010
DOI
10.1371/journal.pone.0012765
Publisher Statement
© 2010 Deans et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This document was originally published in PLOS ONE.
Citation Information
Michael R. Dean, Jonathan M. Peterson and G. William Wong. "Mammalian Otolin: A Multimeric Glycoprotein Specific to the Inner Ear that Interacts with Otoconial Matrix Protein Otoconin-90 and Cerebellin-1" PLOS ONE Vol. 5 Iss. 9 (2010) p. e12765 ISSN: 1932-6203
Available at: http://works.bepress.com/jonathan-peterson/14/