Biomedical Engineering Reference
In-Depth Information
These three cytoplasmic PCP genes also differ from Fz/Vang/Fmi in
terms of the temporal requirement for their function (Strutt & Strutt, 2007).
Fz/Vang/Fmi function is required from
6 h APF in fly pupal
development for proper planar polarization of the wing tissue. Although they
may act earlier, proper polarization can be achievedwhen Pk andDsh function
are present only after 16 h APF.
Multiple lines of evidence indicate that the cytoplasmic core proteins
stabilize or enhance accumulation of intercellular complexes, and because
they act within the cell, the simplest explanation is that they act cell auton-
omously. The first comes from genetic experiments in which any one of
these three PCP proteins is overexpressed within a clone of wing cells
(
Bastock et al., 2003; Das et al., 2004; Tree, Shulman, et al., 2002
). A
substantial enhancement of protein localization at adherens junctions
within the clone is observed, for most, if not all, other core PCP
proteins. This suggests that these cytoplasmic factors can reinforce stable
intercellular complex formation, either directly or indirectly. Among
these, it is especially interesting to point out that overexpressing Dgo
autonomously enhances clustering of Fmi molecules at the adherens
junction (
Jenny, Reynolds-Kenneally, Das, Burnett, & Mlodzik, 2005
).
Notably, accumulation of PCP complexes is similarly nonuniform at
wild-type junctions. These clusters likely resemble the recently reported
discrete membrane domains undergoing unique protein turnover
dynamics (
Strutt, Warrington, & Strutt, 2011
).
These observations of enhancement of cortical PCP complex localiza-
tion do not offer any direct hints toward how the cytoplasmic PCP proteins
promote the amplification of asymmetry during polarization. One hint
comes from the finding that at least some of these factors demonstrate
mutually exclusive biochemical interactions. For example, both Pk and
Dgo bind to Dsh
in vitro
. However, the Dsh-Pk interaction is strongly
inhibited by the presence of Dgo, likely through competition for the same
Dsh binding site (
Jenny et al., 2005
). We are just at the beginning of under-
standing what is likely a complex core PCP protein interaction network.
Furthermore, it will be a considerable challenge to correlate the
in vitro
findings to the physiological roles of any specific interaction
in vivo
, where
the network structure includes feedback mechanisms making predictions of
pattern outcomes nonintuitive. We postulate that at least some of these
protein interactions involving the cytoplasmic core PCP factors mediate
the cell-autonomous repulsive interactions between the Fz-containing distal
complex and the Vang-containing proximal complex.
