title: Wnt signalling: the case of the 'missing' G-protein.
abstract: Wnt signalling remains a hot topic for cell signalling sleuthhounds. The trail of signalling downstream of the seven-transmembrane segment Frizzleds, which bind Wnt ligands, is replete of clues [e.g. LPR5/6 (lipoprotein receptor-related protein 5/6), G-proteins or Dishevelled] and yet remains the 'final problem'. Although the heptahelical nature of Frizzleds places them well within a populous family of G-protein-coupled receptors, resistance to this theme has waxed and waned amid increasing demands for 'proof'. The Wnt Homepage (http://www.stanford.edu/group/nusselab/cgi-bin/wnt/) has acted as a dynamic real-time arbiter of the controversy, highlighted by the appearance and later the disappearance of the G-protein from its central diagramming and tabulations. A recent publication in this issue of the Biochemical Journal offers a solution to the 'final problem', demonstrating under native conditions that Frizzleds expressed in mammalian brain preparations act functionally to catalyse guanine-nucleotide exchange in response to stimulation with Wnt3a. Lensed from the fictional character of Sherlock Holmes, The Case of the Missing G-Protein is investigated.
authors.affiliation: Department of Molecular Pharmacology, Diabetes & Metabolic Diseases Research Center, Stony Brook University, NY 11794-8651, USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Malbon
mesh_terms: D000818:Animals; D051157:Frizzled Receptors / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D006150:Guanine Nucleotides; D051153:Wnt Proteins; D019204:GTP-Binding Proteins