Biomedical Engineering Reference
In-Depth Information
accumulate in a synergistic way. Further, all of the core group proteins must be
functional for the normal asymmetric accumulation to occur (
Fig. 1.2A
).
4.1. Interactions of transmembrane proteins
The distal edge of one cell is juxtaposed to the proximal edge of the neigh-
boring cell distal to it (
Fig. 1.6
). This provides an interface for asymmetric
signaling that is likely to be part of a positive feedback mechanism that
helps establish the distinct proximal and distal membrane domains. Several
groups have proposed that interactions between the three
fz/stan
pathway
proteins that are transmembrane proteins, Fz, Vang, and Stan, are a key
to this process (
Chen et al., 2008; Strutt & Strutt, 2008; Wu & Mlodzik,
2008
). A variety of data support these models. These include biochemical
evidence for an interaction and
in situ
protein localization studies. There
are, however, differences between the experimental results and the
interpretations reported by these groups, so at the current time, there is
not a consensus for how these proteins interact and provide for polarized
signaling. It will be important for these differences to be resolved;
however, the general conclusion that heterotypic protein interactions
provide the basis for the intercellular signaling between cells appears to be
on solid ground.
F-actin
Mwh
Fy
In
Fr tz
Distal target
Dsh
Pk
Dgo
Figure 1.6 A possible model for PCP protein action in wing cells. Two neighboring cells
are diagramed. Proteins on the distal membrane of one cell (Fz and Stan) interact with
proteins on the proximal membrane of the neighboring cell (Vang and Stan). The core
transmembrane proteins recruit the cytoplasmic core proteins (Dsh, Dgo, and Pk). The
PPE proteins are recruited to the proximal side where In recruits Mwh. Mwh inhibits the
actin cytoskeleton in the distal part of the cell. Dsh activates an activator of the actin
cytoskeleton distally. For simplicity, only one of the feedback interactions between
cytoplasmic proteins is drawn (Pk inhibiting Dsh on the distal side).
