title: WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3.
abstract: The wingless/int1 (WNT)/Frizzled (FZD) signalling pathway controls numerous cellular processes such as proliferation, differentiation, cell-fate decisions, migration and plays a crucial role during embryonic development. Nineteen mammalian WNTs can bind to 10 FZDs thereby activating different downstream pathways such as WNT/β-catenin, WNT/planar cell polarity and WNT/Ca(2+) . However, the mechanisms of signalling specification and the involvement of heterotrimeric G proteins are still unclear. Disturbances in the pathways can lead to various diseases ranging from cancer, inflammatory diseases to metabolic and neurological disorders. Due to the presence of seven-transmembrane segments, evidence for coupling between FZDs and G proteins and substantial structural differences in class A, B or C GPCRs, FZDs were grouped separately in the IUPHAR GPCR database as the class FZD within the superfamily of GPCRs. Recently, important progress has been made pointing to a direct activation of G proteins after WNT stimulation. WNT/FZD and G protein coupling remain to be fully explored, although the basic observation supporting the nature of FZDs as GPCRs is compelling. Because the involvement of different (i) WNTs; (ii) FZDs; and (iii) intracellular binding partners could selectively affect signalling specification, in this review we present the current understanding of receptor/ligand selectivity of FZDs and WNTs. We pinpoint what is known about signalling specification and the physiological relevance of these interactions with special emphasis on FZD-G protein interactions.
authors.affiliation: Section of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J P
authors.initials: JP
authors.lastname: Dijksterhuis
authors.forename: J
authors.initials: J
authors.lastname: Petersen
authors.forename: G
authors.initials: G
authors.lastname: Schulte
mesh_terms: D000818:Animals; D051157:Frizzled Receptors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D051153:Wnt Proteins; D019204:GTP-Binding Proteins
keywords: Dishevelled; Frizzled; GPCR; WNT; heterotrimeric G proteins
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