Evolution and function of Tmc genes in mammalian hearing

Auditory sensation in the mammalian inner ear requires mechanosensitive hair cells and an elaborate array of molecules that form the sensory transduction machinery. Several components of this machine have been identified, yet how the ensemble functions in harmony to enable the sense of hearing has not been clarified. We review recent evidence supporting the role of key transduction molecules and focus on TMC1 and TMC2, pore-forming proteins at the heart the mechanosensory device. We consider how vertebrate TMCs changed during evolution and how they function in concert with other components of the transduction apparatus. We also examine the role of TMCs in non-mammalian systems to gain insight into common themes for TMC function and properties unique to mammalian hair cell TMCs. Although the tempo of discovery has accelerated, important questions remain which will need to be addressed for a comprehensive understanding of mechanosensory transduction in the mammalian inner ear.