Sci. Signal., 24 August 2010
Internal DecisionsFrizzled (Fz) proteins are receptors that trigger two different types of signaling pathways. The first, canonical signaling, requires that Fz be bound by its ligand Wnt and results in the expression of target genes. The second, planar cell polarity (PCP), regulates cell position in tissues, does not seem to require Wnt, and depends on the subcellular localization of Fz. What drives the "decision" for Fz to trigger canonical rather than PCP signaling is unclear. By examining protein-protein interactions in vitro and in Drosophila wings, Purvanov et al. showed that the heterotrimeric G protein Go, which is downstream of Fz, bound to and activated Rab5, which was required for the endocytosis of Fz. Regulation of the subsequent trafficking of Fz determined the signaling outcome, with interactions of Fz with Rab4 and Rab11, which mediate recycling of Fz and other receptors, disrupting canonical signaling and promoting PCP signaling. Hence, these pathways might be mutually exclusive.
Citation: V. Purvanov, A. Koval, V. L. Katanaev, A Direct and Functional Interaction Between Go and Rab5 During G Protein–Coupled Receptor Signaling. Sci. Signal. 3, ra65 (2010).
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