Calcium signaling and genetic rare diseases: An auditory perspective

Deafness is a highly heterogeneous disorder which stems, for 50%, from genetic origins. Sensory transduction relies mainly on sensory hair cells of the cochlea, in the inner ear. Calcium is key for the function of these cells and acts as a fundamental signal transduction. Its homeostasis depends on three factors: the calcium influx, through the mechanotransduction channel at the apical pole of the hair cell as well as the voltage-gated calcium channel at the base of the cells; the calcium buffering via Ca²⁺-binding proteins in the cytoplasm, but also in organelles such as mitochondria and the reticulum endoplasmic mitochondria-associated membranes with specialized proteins; and the calcium extrusion through the Ca-ATPase pump, located all over the plasma membrane. In addition, the synaptic transmission to the central nervous system is also controlled by calcium. Genetic studies of inherited deafness have tremendously helped understand the underlying molecular pathways of calcium signaling. In this review, we discuss these different factors in light of the associated genetic diseases (syndromic and non-syndromic deafness) and the causative genes.