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preferentially binds Fz, rather than Vang, when present in excess. This
differential affinity is in accordance with the observation that when pro-
duced in excess, Fmi molecules behave as though associated with Vang
and recruit Fmi-Fz complexes on the other side of the adherens junction
( Chen et al., 2008 ). Furthermore, Strutt and Strutt observed that stable inter-
cellular Fmi complexes form when neither cell expresses Vang and one cell
expresses Fz, but not when neither cell expresses Fz and one expresses Vang.
Because one side of the complex must have Fz, this result is consistent with
the model of Chen et al. in which Fz induces a form of Fmi that selectively
interacts with Fmi that is or is not associated with Vang.
The debate about how Fz and Vang recruit each other across intercellular
boundaries is likely to continue as additional studies explore the interactions
between Fz, Vang, and Fmi at the adherens junctions. We expect that
elucidating the biochemical characteristics and conformational nature of
Fmi dimers will be a key milestone pushing our understanding of planar
polarity propagation to a new mechanistic level.
4.3. Autonomous choices: Focusing within a single cell
While much has been learned about the mutual recruitment between the
distal Fz complexes and proximal Vang complexes ( Fig. 2.2A ), it has yet
to be rigorously determined whether these cross-junctional interactions
can be solely responsible for achieving asymmetric protein localization in
a self-organizing way. Mathematical modeling can simulate the acquisi-
tion of PCP protein asymmetry based on the mutual recruitment between
Fz- and Vang-containing complexes in neighboring cells. To do so, the
model must include repulsive interactions between the proximal and distal
complexes within the same cell, and indeed, data implicating such
interactions in part motivated the initial proposal of the feedback loop
( Tree,Shulman,etal.,2002 ). Additional genetic analyses have begun to
define the component requirement and mechanism of this cell-
autonomous repulsion ( Fig. 2.2B ). Three cytoplasmic core PCP genes,
Dsh, Dgo, and Pk, which are not required for the assembly of asymmetric
Fz-, Vang-, and Fmi-containing intercellular complexes, are almost
certainly playing essential roles in the cell-autonomous repulsion between
proximal and distal complexes required for amplifying asymmetry in a
self-organizing fashion. When any of these three genes' function is
compromised, the mutant cell loses PCP protein asymmetry in a largely
cell-autonomous way.
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