title: Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta.
abstract: Dishevelled family proteins are multidomain intracellular transducers of Wnt signals. Ectopically expressed mammalian Dishevelled 2 (Dvl-2) activates downstream signalling and localises to cytoplasmic puncta. It has been suggested that these Dvl-2-containing structures correspond to intracellular vesicles and may be involved in the Wnt signal transduction process. We report that cytoplasmic puncta are primarily formed in cells expressing Dvl-2 at high levels. Lower levels of expression can activate signalling without forming puncta. The structures do not localise with markers of the early or late endocytic pathway and time-lapse analysis demonstrates that Dvl-2 puncta move in a random fashion over short distances but do not originate from the plasma membrane. Based on our findings, we propose that Dvl-2 puncta are protein aggregates that are not required for signalling.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Smalley
authors.forename: Nathalie
authors.initials: N
authors.lastname: Signoret
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Alan
authors.initials: A
authors.lastname: Tilley
authors.forename: Anthony
authors.initials: A
authors.lastname: Hann
authors.forename: Ken
authors.initials: K
authors.lastname: Ewan
authors.forename: Yanning
authors.initials: Y
authors.lastname: Ding
authors.forename: Hugh
authors.initials: H
authors.lastname: Paterson
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Dale
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004285:Dogs; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects; D060149:Tetraspanin 30; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D033921:Vesicular Transport Proteins; D051153:Wnt Proteins; C093846:early endosome antigen 1