The frizzled/stan Pathway and Planar Cell Polarity in the Drosophila Wing - Current Topics in Developmental Biology - page 22

6. DOWNSTREAM EFFECTORS
6.1. Planar polarity effector genes
The three PPE proteins, In, Fy, and Frtz, are recruited to the proximal side of
wing cells in a core group-dependent manner ( Fig. 1.2A )( Adler et al., 2004;
Strutt & Warrington, 2008 ). For example, in an fz mutant, the asymmetric
accumulation of In and Frtz is lost and indeed these proteins are found at
much lower levels in such a mutant. It seems likely that at least one of
these proteins is recruited by binding (either directly or indirectly) to
either Pk or Vang, the two proximal specific proteins. As is the case for the
upstream genes, each of the PPE genes needs to be functional for the
proteins to preferentially accumulate on the proximal side ( Adler et al.,
2004; Strutt & Warrington, 2008 ). In contrast to the situation with the
upstream genes, the overexpression of PPE genes has not been reported to
produce a gain of function PCP phenotype ( Park et al., 1996 ). This seems
somewhat surprising as overexpression often leads to a loss in the spatially
restricted accumulation of a protein, which results in altered function. One
possibility is that the overexpression does not saturate the system that
localizes the proteins to the proximal side. This seems unlikely. A more
attractive possibility is that a protein that is not properly localized is not
active due to a lack of one or more binding partners.
6.2. mwh
The mwh gene, which by epistasis tests is the most downstream member of
the fz/stan pathway, also accumulates on the proximal side of wing cells and
this is dependent on both core and PPE proteins and genes ( Fig. 1.2A )( Strutt
& Warrington, 2008; Yan et al., 2008 ). Two papers have suggested possible
mechanisms. In one, Lu and colleagues found that Mwh and In directly
interacted and they suggested that In on the proximal side of wing cells
recruited Mwh ( Lu et al., 2010 ). In the other, Strutt and colleagues
found that Mwh was phosphorylated in a PPE-dependent manner and
suggested this was important in the action of Mwh in ensuring a single
distally pointing hair is formed ( Strutt & Warrington, 2008 ). These two
mechanisms are, of course, not mutually exclusive. A variety of results
argue that Mwh serves as an inhibitor of the actin cytoskeleton ( Fig. 1.6 ).
How this is accomplished is unclear, but it is worth noting that the amino
terminal half of the large Mwh protein contains and a G protein-binding