title: Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Deans
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Peterson
authors.forename: G William
authors.initials: GW
authors.lastname: Wong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D003001:Cloning, Molecular; D007758:Ear, Inner / Q000737:chemistry / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D051379:Mice / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017685:Oncorhynchus keta; D011485:Protein Binding; D055503:Protein Multimerization; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D002135:Calcium-Binding Proteins; C092370:Cbln1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C512837:Oc90 protein, mouse; D011498:Protein Precursors; C449659:otolin-1