title: Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos.
abstract: E-cadherin is a ubiquitous component of lateral membranes in epithelial tissues and is required to form the first lateral membrane domains in development. Here, we identify ankyrin-G as a molecular partner of E-cadherin and demonstrate that ankyrin-G and beta-2-spectrin are required for accumulation of E-cadherin at the lateral membrane in both epithelial cells and early embryos. Ankyrin-G binds to the cytoplasmic domain of E-cadherin at a conserved site distinct from that of beta-catenin. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton. In addition to restricting the membrane mobility of E-cadherin, ankyrin-G and beta-2-spectrin also are required for exit of E-cadherin from the trans-Golgi network in a microtubule-dependent pathway. Ankyrin-G and beta-2-spectrin co-localize with E-cadherin in preimplantation mouse embryos. Moreover, knockdown of either ankyrin-G or beta-2-spectrin in one cell of a two-cell embryo blocks accumulation of E-cadherin at sites of cell-cell contact. E-cadherin thus requires both ankyrin-G and beta-2-spectrin for its cellular localization in early embryos as well as cultured epithelial cells. We have recently reported that ankyrin-G and beta-2-spectrin collaborate in biogenesis of the lateral membrane ( Kizhatil, K., Yoon, W., Mohler, P. J., Davis, L. H., Hoffman, J. A., and Bennett, V. (2007) J. Biol. Chem. 282, 2029-2037 ). Together with the current findings, these data suggest a ankyrin/spectrin-based mechanism for coordinating membrane assembly with extracellular interactions of E-cadherin at sites of cell-cell contact.
authors.affiliation: Howard Hughes Medical Institute, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Kizhatil
authors.forename: Jonathan Q
authors.initials: JQ
authors.lastname: Davis
authors.forename: Lydia
authors.initials: L
authors.lastname: Davis
authors.forename: Jan
authors.initials: J
authors.lastname: Hoffman
authors.forename: Brigid L M
authors.initials: BL
authors.lastname: Hogan
authors.forename: Vann
authors.initials: V
authors.lastname: Bennett
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017487:Ankyrins / Q000172:deficiency / Q000378:metabolism*; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism*; D013049:Spectrin
chemical_list: D000199:Actins; D017487:Ankyrins; D015820:Cadherins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D051176:beta Catenin; D013049:Spectrin; C094681:Ank3 protein, mouse