6
R. Nusse et al.
Fz
Stbm
@ ...........
~
/,
cytoskeleton
0
nUcleUS?/'
Fig. 3. Fz signaling
are required for ligand binding (reviewed in Dohlman et al. 1991),
whereas the CRD of Fz molecules is implicated in ligand binding (see
below).
With regard to effector binding, the Fz proteins lack the most conserved motifs present in almost all G-protein coupled receptors, such as
the Glu/Asp-Arg-TyrlPhe triplet at the C-terminus of the third transmembrane segment (Probst et al. 1992; Wang et al. 1996). This suggests
that Fz proteins may use novel downstream effector pathways, although
there is evidence that at least one Fz member can signal through calcium
release and a G-protein (Slusarski et al. 1997). A further genetic analysis
of this pathway in organisms such as Drosophila and C. elegans will
undoubtedly shed more light on this issue.
1.6 Signaling Downstream of Fz
In genetic tests, dsh, which is also in the W g pathway, is epistatic to fz
(Krasnow and Adler 1994; Krasnow et al. 1995). Recently, it has been