title: Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells.
abstract: Signal propagation from the cell membrane to a promoter can induce gene expression. To examine signal transmission through sub-cellular compartments and its effect on transcription levels in individual cells within a population, we used the Wnt/β-catenin signaling pathway as a model system. Wnt signaling orchestrates a response through nuclear accumulation of β-catenin in the cell population. However, quantitative live-cell measurements in individual cells showed variability in nuclear β-catenin accumulation, which could occur in two waves, followed by slow clearance. Nuclear accumulation dynamics were initially rapid, cell cycle independent and differed substantially from LiCl stimulation, presumed to mimic Wnt signaling. β-catenin levels increased simultaneously at adherens junctions and the centrosome, and a membrane-centrosome transport system was revealed. Correlating β-catenin nuclear dynamics tocyclin D1transcriptional activation showed that the nuclear accumulation rate of change of the signaling factor, and not actual protein levels, correlated with the transcriptional output of the pathway.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Pinhas
authors.initials: P
authors.lastname: Kafri
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hasenson
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Kanter
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sheinberger
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Kinor
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Yunger
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Institute of Nanotechnology, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Yaron
authors.identifier: 0000-0002-8017-948X
authors.initials: Y
authors.lastname: Shav-Tal
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059010:Single-Cell Analysis; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin; D019938:Cyclin D1; D051722:ADAM Proteins; C068490:ADAM8 protein, human; D018021:Lithium Chloride
keywords: cell biology; chromosomes; genes; human; live-cell imaging; signalling; transcription; transcription factor dynamics; transcriptional kinetics