Biomedical Engineering Reference
In-Depth Information
4.2. Intracellular proteins
It is likely that in addition to intercellular signaling an intracellular feedback
system plays an important role in the formation of the proximal and distal
protein domains (
Amonlirdviman et al., 2005; Tree et al., 2002
). Several
interactions have been detected between proximal and distal proteins. For
example, Dsh and Vang, Dsh and Pk, Dgo and Pk, and Dgo and Vang
have been found to interact (
Bastock et al., 2003; Das et al., 2004; Jenny
et al., 2003; Tree et al., 2002
). The interaction between proximal and
distal proteins appears to be negative. Hence, a negative interaction
between Pk and Dsh could prevent Dsh from accumulating on the
proximal side and Pk from accumulating on the distal side (
Fig. 1.6
). Such
models suggest the interactions be dependent on cellular location. For
example, when Pk and Dsh interact on the proximal side of the cell, Dsh
would be lost. A hint as to how this may work comes from experiments
on mice where it was found that a Smurf ubiquitin ligase targets Pk for
proteasome-mediated degradation (
Narimatsu et al., 2009
). As of yet, no
equivalent experimental evidence has been published that a similar
mechanism works in the fly (e.g., Pk interacting with Dsh results in Dsh
being degraded in a proteasomal-dependent mechanism), but it is
certainly an attractive hypothesis to explain the negative protein interactions.
4.3. Wnts in fly PCP?
The
fz
gene family gets its name from the PCP phenotype of its founding
member, but Fz proteins are very well known as a family of receptors for
Wnt ligands (
Bhanot et al., 1996
). However, in Drosophila, studies have
failed to detect PCP phenotypes in genotypes where one or multiple Wnts
are lost due to mutation (
Chen et al., 2008; Lawrence, Casal, & Struhl,
2002
). In vertebrate tissues, there is substantial evidence for Wnt ligands
functioning in PCP (see
Goodrich & Strutt, 2011; Wang & Nathans,
2007
; other articles in this volume).
4.4. Mechanisms for the formation of PCP protein complexes
There are several possible mechanisms that could be responsible for the asym-
metric accumulation of PCP proteins on the proximal or distal membranes.
One would be for the proteins to be preferentially synthesized at those loca-
tions (
Berleth et al., 1988; Davis & Ish-Horowicz, 1991; Macdonald & Struhl,
1988
). A second would be the directed trafficking of the proteins to the
correct side of the cell (
Shimada, Yonemura, Ohkura, Strutt, & Uemura,
