title: Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan.
abstract: Drosophila melanogaster Armadillo plays two distinct roles during development. It is a component of adherens junctions, and functions as a transcriptional activator in response to Wingless signaling. In the current model, Wingless signal causes stabilization of cytoplasmic Armadillo allowing it to enter the nucleus where it can activate transcription. However, the mechanism of nuclear import and export remains to be elucidated. In this study, we show that two gain-of-function alleles of Armadillo activate Wingless signaling by different mechanisms. The S10 allele was previously found to localize to the nucleus, where it activates transcription. In contrast, the Delta Arm allele localizes to the plasma membrane, and forces endogenous Arm into the nucleus. Therefore, Delta Arm is dependent on the presence of a functional endogenous allele of arm to activate transcription. We show that Delta Arm may function by titrating Axin protein to the membrane, suggesting that it acts as a cytoplasmic anchor keeping Arm out of the nucleus. In axin mutants, Arm is localized to the nuclei. We find that nuclear retention is dependent on dTCF/Pangolin. This suggests that cellular distribution of Arm is controlled by an anchoring system, where various nuclear and cytoplasmic binding partners determine its localization.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Tolwinski
authors.forename: E
authors.initials: E
authors.lastname: Wieschaus
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D051186:Armadillo Domain Proteins; D060466:Axin Protein; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005260:Female; D006609:High Mobility Group Proteins / Q000378:metabolism* / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D051155:Wnt1 Protein
chemical_list: C495305:ARM protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; D060466:Axin Protein; C118000:Axn protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila