Vezatin, a novel transmembrane protein, bridges myosin VIIA to the cadherin-catenins complex

Defects in myosin VIIA are responsible for deafness in the human and mouse. The role of this unconventional myosin in the sensory hair cells of the in ner ear is not yet understood. Here we show that the C-terminal FERM domain of myosin VIIA binds to a novel transmembrane protein, vezatin, which we i dentified by a yeast two-hybrid screen. Vezatin is a ubiquitous protein of adherens cell-cell junctions, where it interacts with both myosin VHA and t he cadherin-catenins complex. Its recruitment to adherens junctions implica tes the C-terminal region of alpha -catenin, Taken together, these data sug gest that myosin VIIA, anchored by vezatin to the cadherin-catenins complex , creates a tension force between adherens junctions and the actin cytoskel eton that is expected to strengthen cell-cell adhesion. In the inner ear se nsory hair cells vezatin is, in addition, concentrated at another membrane- membrane interaction site, namely at the fibrillar links interconnecting th e bases of adjacent stereocilia, In myosin VIIA-defective mutants, inactivi ty of the vezatin-myosin VIIA complex at both sites could account for splay ing out of the hair cell stereocilia.