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 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 identified 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 α‐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 fibrillar 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.

[1]  C. Petit,et al.  Unconventional Myosin VIIA Is a Novel A-kinase-anchoring Protein* , 2000, The Journal of Biological Chemistry.

[2]  R. Geisler,et al.  Mariner is defective in myosin VIIA: a zebrafish model for human hereditary deafness. , 2000, Human molecular genetics.

[3]  B. Geiger,et al.  A role for alpha-and beta-catenins in bacterial uptake. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  U. Wolfrum,et al.  Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells. , 2000, Cell motility and the cytoskeleton.

[5]  Elaine Fuchs,et al.  Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion , 2000, Cell.

[6]  B. Geiger,et al.  A role for a- and b-catenins in bacterial uptake , 2000 .

[7]  D. Shore,et al.  Cingulin Contains Globular and Coiled-Coil Domains and Interacts with Zo-1, Zo-2, Zo-3, and Myosin , 1999, The Journal of cell biology.

[8]  M. Titus A class VII unconventional myosin is required for phagocytosis , 1999, Current Biology.

[9]  Oliver Tn,et al.  Tails of unconventional myosins. , 1999 .

[10]  K. Steel,et al.  Myosin VIIa Participates in Opsin Transport through The Photoreceptor Cilium , 1999, The Journal of Neuroscience.

[11]  Richard Goodyear,et al.  The Ankle-Link Antigen: an Epitope Sensitive to Calcium Chelation Associated with the Hair-Cell Surface and the Calycal Processes of Photoreceptors , 1999, The Journal of Neuroscience.

[12]  T. N. Oliver,et al.  Tails of unconventional myosins , 1999, Cellular and Molecular Life Sciences (CMLS).

[13]  C. L. Adams,et al.  Cytomechanics of cadherin-mediated cell-cell adhesion. , 1998, Current opinion in cell biology.

[14]  H. Schwarz,et al.  Targeting of the myosin-I myr 3 to intercellular adherens type junctions induced by dominant active Cdc42 in HeLa cells. , 1998, Journal of cell science.

[15]  Cynthia L. Adams,et al.  Mechanisms of Epithelial Cell–Cell Adhesion and Cell Compaction Revealed by High-resolution Tracking of E-Cadherin– Green Fluorescent Protein , 1998, The Journal of cell biology.

[16]  S. C. Liu,et al.  The FERM domain: A unique module involved in the linkage of cytoplasmic proteins to the membrane , 1998 .

[17]  Xinran Liu,et al.  Mutant myosin VIIa causes defective melanosome distribution in the RPE of shaker-1 mice , 1998, Nature Genetics.

[18]  Y. Raphael,et al.  Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. , 1998, Science.

[19]  C. Morton,et al.  Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. , 1998, Science.

[20]  K. Steel,et al.  Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells. , 1998, Development.

[21]  V. Mermall,et al.  Unconventional myosins in cell movement, membrane traffic, and signal transduction. , 1998, Science.

[22]  D. S. Williams,et al.  Myosin VIIa as a common component of cilia and microvilli. , 1998, Cell motility and the cytoskeleton.

[23]  K. Steel,et al.  Myosin VIIA Is Required for Aminoglycoside Accumulation in Cochlear Hair Cells , 1997, The Journal of Neuroscience.

[24]  S. Eaton Planar polarization of Drosophila and vertebrate epithelia. , 1997, Current opinion in cell biology.

[25]  A. Hyman,et al.  Motor proteins of the eukaryotic cytoskeleton. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C. Petit,et al.  Expression of myosin VIIA during mouse embryogenesis , 1997, Anatomy and Embryology.

[27]  D. Corey,et al.  Unconventional Myosins in Inner-Ear Sensory Epithelia , 1997, The Journal of cell biology.

[28]  C. Petit,et al.  The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene , 1997, Nature Genetics.

[29]  B. Gumbiner,et al.  Molecular and functional analysis of cadherin-based adherens junctions. , 1997, Annual review of cell and developmental biology.

[30]  D. S. Williams,et al.  Myosin VIIa, the product of the Usher 1B syndrome gene, is concentrated in the connecting cilia of photoreceptor cells. , 1997, Cell motility and the cytoskeleton.

[31]  S. J. Smith,et al.  Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion , 1996, The Journal of cell biology.

[32]  D. Corey,et al.  Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B. , 1996, Genomics.

[33]  J. Sahel,et al.  Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. , 1996, Human molecular genetics.

[34]  W J Nelson,et al.  Mechanism for transition from initial to stable cell-cell adhesion: kinetic analysis of E-cadherin-mediated adhesion using a quantitative adhesion assay , 1996, The Journal of cell biology.

[35]  Norma B. Slepecky,et al.  Structure of the Mammalian Cochlea , 1996 .

[36]  J. Santos-Sacchi,et al.  Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D L Rimm,et al.  Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M. Bähler,et al.  A novel mammalian myosin I from rat with an SH3 domain localizes to Con A-inducible, F-actin-rich structures at cell-cell contacts , 1995, The Journal of cell biology.

[39]  Steve D. M. Brown,et al.  Defective myosin VIIA gene responsible for Usher syndrome type IB , 1995, Nature.

[40]  K. Steel,et al.  A type VII myosin encoded by the mouse deafness gene shaker-1 , 1995, Nature.

[41]  B. Rost,et al.  Transmembrane helices predicted at 95% accuracy , 1995, Protein science : a publication of the Protein Society.

[42]  Karen P. Steel,et al.  The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells , 1995, Nature Genetics.

[43]  M. Itoh,et al.  Cell-to-cell adherens junction formation and actin filament organization: similarities and differences between non-polarized fibroblasts and polarized epithelial cells. , 1995, Journal of cell science.

[44]  H Weissig,et al.  Assembly of the cadherin-catenin complex in vitro with recombinant proteins. , 1994, Journal of cell science.

[45]  S. Ishihara,et al.  The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules , 1994, The Journal of cell biology.

[46]  R. Kemler,et al.  A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated. , 1994, Cell adhesion and communication.

[47]  R. Kemler From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. , 1993, Trends in genetics : TIG.

[48]  M. Ringwald,et al.  Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[49]  M. Takeichi,et al.  Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. , 1989, Cell regulation.

[50]  S. Hirohashi,et al.  Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. , 1989, Cancer research.

[51]  M. Takeichi,et al.  Cell binding function of E‐cadherin is regulated by the cytoplasmic domain. , 1988, The EMBO journal.

[52]  G. von Heijne,et al.  Topogenic signals in integral membrane proteins. , 1988, European journal of biochemistry.

[53]  D. Cotanche,et al.  Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated , 1988, The Journal of cell biology.

[54]  D. DeRosier,et al.  Actin Filaments , Stereocilia , and Hair Cells of the Bird Cochlea . V . How the Staircase Pattern of Stere iliary Lengths Is Generated , 2002 .

[55]  N. Hirokawa,et al.  Interactions between actin filaments and between actin filaments and membranes in quick-frozen and deeply etched hair cells of the chick ear , 1982, The Journal of cell biology.

[56]  G. Danscher A Photochemical Method for Light and Electronmicroscopy , 1981 .