Phase separation-mediated condensation of Whirlin-Myo15-Eps8 stereocilia tip complex
Hair cells in the inner ear are specialized mechanoreceptor cells that detect sound and convert them through mechanical-electrical transduction. The organelles on hair cells that perform this function are called hair bundles or stereocilia, which are comprised of actin bundles. Several other proteins have been identified in Stereocilia at very high densities in the tip region; furthermore, mutations of several of these proteins have been associated with deafness. Lin et al. sought to understand the role of these proteins in the tip region, their complex interactions, and how they regulated actin bundling. These investigators discovered that one of these proteins, Whirlin, forms condensate due to liquid-liquid phase separations, and the level of condensation was amplified in the presence of other proteins like myosin15 and Eps8. Using x-ray crystallography and molecular cloning approaches they identified essential domains necessary for the multivalent interactions between these three proteins and determined that a prominent mutation in myosin 15 that resulted in deafness altered complex formation and inhibited condensation. Interestingly, the investigators determined that this complex may function in part by enhancing Eps8 ability to promote actin bundling and could be an underlying mechanism for hearing loss. Cytoskeleton’s actin protein (Cat. # AKL99) was essential for these functional studies that investigated actin bundling regulation by these critical proteins in the stereocilia.
Proposed model for the tip density assembly mediated by phase separation of the tip complex.
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