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.
Commentary| January 14 2011
Wnt signalling: the case of the ‘missing’ G-protein
Craig C. Malbon
Craig C. Malbon 1
1Department of Molecular Pharmacology, University Medical Center and the Diabetes & Metabolic Diseases Research Center, School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, U.S.A.
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Craig C. Malbon; Wnt signalling: the case of the ‘missing’ G-protein. Biochem J 1 February 2011; 433 (3): e3–e5. doi: https://doi.org/10.1042/BJ20102111
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