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

Abstract

contributed equally to this work 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 inner 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 identi®ed by a yeast two-hybrid screen. Vezatin is a ubiquitous protein of adherens cell±cell junctions, where it interacts with both myosin VIIA and the cadherin±catenins complex. Its recruitment to adherens junctions implicates the C-terminal region of a-catenin. Taken together, these data suggest that myosin VIIA, anchored by vezatin to the cadherin±catenins complex, creates a tension force between adherens junctions and the actin cytoskeleton that is expected to strengthen cell±cell adhesion. In the inner ear sensory hair cells vezatin is, in addition, concentrated at another membrane±membrane interaction site, namely at the ®brillar links interconnecting the bases of adjacent stereocilia. In myosin VIIA-defective mutants, inactivity of the vezatin±myosin VIIA complex at both sites could account for splaying out of the hair cell stereocilia.

Cytoskeletal dynamics and spermatogenesis

“…Studies in other epithelia suggest the participation of myosin VIIa during AJ formation. For instance, in MDCK cells, myosin VIIa is recruited to the cadherin-based protein complex together with vezatin, where it is proposed to generate a tensile force between the plasma membrane and the actin cytoskeleton to strengthen cell -cell adhesion (Kussel-Andermann et al 2000). The significance of myosin VIIa at the ES is yet to be investigated.…”

All kinesin superfamily protein, KIF, genes in mouse and human

“…The search for adaptor proteins other than kinesin light chains and kinectin (100) has begun (8,9). The trend has extended to myosin research (101). To elucidate the mechanism of intracellular transport, the regulation of cargo binding is also an important problem.…”

Vezatin, a ubiquitous protein of adherens cell–cell junctions, is exclusively expressed in germ cells in mouse testis

“…In various epithelial cells, vezatin, a second transmembrane protein of adherens cell-cell junctions based on the Ca 2C -dependent cadherin family, anchors unconventional myosin VIIa to the cadherin-catenin complex (Kussel-Andermann et al 2000, Hyenne et al 2005. At the site of adherens junctions, vezatin could modulate cell-cell adhesion by creating a tension between the plasma membrane and the actin cytoskeleton.…”