An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling.
Armadillo, the Drosophila homologue of vertebrate beta-catenin, plays a pivotal role both in Wingless signaling and in assembly of adherens junctions. We performed the first in vivo structure-function study of an adherens junction protein, by generating and examining a series of Armadillo mutants in the context of the entire animal. We tested each mutant by assaying its biological function, its ability to bind proteins that normally associate with Armadillo in adherens junctions, its cellular localization, and its pattern of phosphorylation. We mapped the binding sites for DE-cadherin and alpha-catenin. Although these bind to Armadillo independently of each other, binding of each is required for the function of adherens junctions. We identified two separate regions of Armadillo critical for Wingless signaling. We demonstrated that endogenous Armadillo accumulates in the nucleus and provide evidence that it may act there in transducing Wingless signal. We found that the Arm repeats, which make up the central two-thirds of Armadillo, differ among themselves in their functional importance in different processes. Finally, we demonstrated that Armadillo's roles in adherens junctions and Wingless signaling are independent. We discuss the potential biochemical role of Armadillo in each process.
Orsulic
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S
Department of Biology, University of North Carolina at Chapel Hill 27599-3280, USA.
Peifer
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M
D000483:Alleles; D000818:Animals; D051186:Armadillo Domain Proteins; D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D004247:DNA; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D007301:Insect Hormones / Q000737:chemistry / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; D051178:alpha Catenin; D051176:beta Catenin
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; D051178:alpha Catenin; D051176:beta Catenin; C074622:wg protein, Drosophila; D004247:DNA