Biomedical subjects

B M Gumbiner

Publications and source records attributed to B M Gumbiner.

3 recordsLinked to original sources

PubMed1992

Epithelial morphogenesis.

The identification of protein factors, such as epimorphin, scatter factor, and activin, that induce epithelial branching and convergent extension-like movements in embryonic tissues are important breakthroughs in our understanding of the role of mesenchyme in epithelial morphogenesis. Moreover, the development of simple in vitro epithelial cell systems that undergo morphogenesis in response to these factors should provide a means to investigate the cellular and molecular bases of the morphogenetic movements themselves. Although many different cellular processes are involved in such morphogenetic behaviors, cell rearrangement is a particularly intriguing one that will be important to study further. Several considerations lead to the prediction that a dynamic regulation of cell-cell adhesion is likely to play a central role in cell rearrangements and epithelial morphogenesis. Ultimately, a greater issue to be addressed is how the different cellular mechanisms participating in epithelial morphogenesis are coordinated and regulated, so as to generate the diverse patterns found in various epithelia.

Animals↗

PubMed1992

The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.

Three proteins identified by quite different criteria in three different systems, the Drosophila segment polarity gene armadillo, the human desmosomal protein plakoglobin, and the Xenopus E-cadherin-associated protein beta-catenin, share amino acid sequence similarity. These findings raise questions about the relationship among the three molecules and their roles in different cell-cell adhesive junctions. We have found that antibodies against the Drosophila segment polarity gene armadillo cross react with a conserved vertebrate protein. This protein is membrane associated, probably via its interaction with a cadherin-like molecule. This cross-reacting protein is the cadherin-associated protein beta-catenin. Using anti-armadillo and antiplakoglobin antibodies, it was shown that beta-catenin and plakoglobin are distinct molecules, which can coexist in the same cell type. Plakoglobin interacts with the desmosomal glycoprotein desmoglein I, and weakly with E-cadherin. Although beta-catenin interacts tightly with E-cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes. Anti-armadillo antibodies have been further used to determine the intracellular localization of beta-catenin, and to examine its tissue distribution. The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed.

Amino Acid Sequence↗

PubMed1991

Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure.

The transmembrane epithelial cell-cell adhesion protein E-cadherin (uvomorulin) associates via its cytoplasmic domain with three or more proteins whose structure and function are not yet established. The associated proteins, also termed catenins (Ozawa, M., Baribault, H., and Kemler, R. (1989) EMBO J. 8, 1711-1717), are of interest because they may form a link to the cytoskeleton, and/or regulate E-cadherin function. In this report immunoprecipitates of E-cadherin complexes, isolated from Xenopus laevis A6 and Madin-Darby canine kidney cell monolayers, were stringently washed to leave a single very tightly associated protein of approximately 92 kDa. We report on the 92-kDa protein's association with E-cadherin in the presence of various perturbants, its preferential dissociation from the immune complex upon exposure to mixed detergent micelles containing sodium dodecyl sulfate, and its preparative purification to homogeneity. We have additionally found that E-cadherin and its associated proteins may be easily and quantitatively extracted from both subconfluent and fully confluent cells by a variety of mild nonionic detergents made up in isotonic buffers. In contrast, such extractions at short times left most of the cytoskeletal protein fodrin in the insoluble pellet fraction. Western blots of immunoprecipitated E-cadherin complexes failed to detect the presence of fodrin, or that of the cytoskeletal proteins adducin, alpha-actinin, and vinculin. If the E-cadherin-associated protein complex interacts with known proteins of the cell cytoskeleton, such interactions are labile and/or transient.

Animals↗