Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin

A mammal’s sense of hearing and balance are helped by so-called hair cells within the inner ear. These cells are named after their long, hair-like protrusions called stereocilia, and mutations in the genes involved in stereocilia development and maintenance can lead to hearing loss in humans. Damage to the stereocilia caused by excessive exposure to loud noises can also have the same effect. Stereocilia are full of filaments made of a protein called actin. Other proteins called class III myosins and Espin are also both required for normal development of stereocilia. Mutations in the genes that encode these proteins can cause hereditary deafness in humans. However, it remains unclear exactly how these two proteins (myosins and Espin) interact with each other in stereocilia. Using biochemical and structural studies, Liu, Li et al. have now discovered that the so-called ‘tail’ part of the myosins contains a pair of repeated sequences that can each interact with an Espin protein called Espin1. This interaction allows each myosin to cross-link two Espin1 proteins. Espins assemble actin filaments into bundles, and further experiments showed that this cross-linking interaction between myosins and Espins helped this process, which is linked to stereocilia development and maintenance. Mammals actually have two related copies of class III myosins that play overlapping but slightly different roles. The next challenge will be to try to understand the differences between these related proteins, as well as to try to uncover the roles of other forms of Espin in stereocilia.