Assembly of the otoconia complex to the macular sensory epithelium of the vestibule

In the inner ear, specificity of stimulus perception is achieved by associating the sensory epithelia of the three mechanoreceptor organs, the utricle/saccule, cristae, and cochlea, with distinct types of acellular matrices. Only the utricle and saccule have an extremely dense matrix, the otoconial complex, which overlies the sensory epithelium (macula) and provides inertial mass to generate shearing forces essential for the mechanoreceptors to sense gravity and linear acceleration. Such sensation is necessary for spatial orientation and balance. The importance of otoconia is clearly demonstrated by the impact of balance disorders upon the elderly population that involve otoconia degeneration, as well as by canalithiasis and cupulolithiasis, in which otoconia are dislocated. This underscores the need to understand how otoconia are formed and maintained and how to prevent their degeneration. To date, a number of otoconia-related proteins have been identified mostly in mice and bony fish. Although most of these proteins are also present in other structures of the inner ear, a distinct collection of proteins in the macula plus the unique ionic microenvironment of the endolymph near its epithelium likely contribute to the site-specific calcification of otoconia. Based on the current literature and ongoing research, this mini-review postulates a working model of how the otoconia complex is assembled specifically above the macular sensory epithelium of the vestibule. The central hypothesis of this model is that proteins are critical in sequestering calcium for crystallization in the calcium-poor endolymph. The review also sets forth some issues that need to be resolved in the future.