Frizzleds As Wnt Receptors 521 Frizzleds The Discovery

About 20 years ago, the product of int-1, a viral mammary oncogene, was observed to resemble that of the Drosophila melanogaster segment polarity

GPCR Molecular Pharmacology and Drug Targeting: Shifting Paradigms and New Directions,

Edited by Annette Gilchrist

Copyright © 2010 John Wiley & Sons, Inc.

gene wingless [1]. This led to the discovery of the WNT (acronym of wingless and int-1) family of lipoglycoproteins [2, 3] . In parallel, the gene product of the frizzled locus in Drosophila melanogaster was determined to code for a protein with seven potential transmembrane domains and a rather large N-terminus, possibly a G protein-coupled receptor (GPCR) [4] . A mutation in this gene leads to disturbed cuticular patterns of bristles that lend the fly a somewhat "frizzled" appearance, suggesting that frizzled and wingless play related roles in regulation of cell polarity (apparent effects on cuticular cell polarity have also been reported in a FZD6 knockout mouse [5]). It was first surmised [6] and then shown that Drosophila Frizzled2 functions as Wingless receptor, which clearly implied that the Frizzled family of seven transmembrane spanning proteins are WNT receptors [7, 8].

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