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 position al 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