Wnt3a stimulation elicits G protein-coupled receptor properties of mammalian frizzled proteins

Alexey Koval , Vladimir L Katanaev (1)

1 Department of Biology

Receptors of the Frizzled (Fz) family initiate Wnt ligand-dependent signaling controlling multiple steps in organism development and carcinogenesis. Fz proteins possess seven transmembrane domains and their signaling depends on heterotrimeric G proteins in various organisms. However, Fzs constitute a distinct group within the G protein-coupled receptors (GPCR) superfamily, and Fz signaling can be G protein-independent in some experimental setups, leading to concerns about the GPCR nature of these proteins. Here we demonstrate that mammalian Fzs act as GPCRs on heterotrimeric Go/i proteins. Addition of the Wnt3a ligand to rat brain membranes or cultured cells elicits Fz-dependent guanine nucleotide exchange on Go/i. These responses were sensitive to a Wnt antagonist and to pertussis toxin, which decouples the Go/i proteins from their receptors through covalent modification. Our findings provide the long-awaited biochemical proof of the GPCR nature of Fz receptors.

Mots clés: Life Sciences

Alexey Koval, Vladimir L Katanaev. Wnt3a stimulation elicits G protein-coupled receptor properties of mammalian frizzled proteins. Biochemical Journal, 2011, 433 (3), pp.435-440. ⟨10.1042/BJ20101878⟩. ⟨hal-00558102⟩