Biomedical Engineering Reference
In-Depth Information
overcome entropy. In this section, we discuss the active mechanisms
through which such asymmetry is achieved and maintained.
4.1. Required components as revealed by genetics
As discovered in the
Drosophila
wing epithelium, a well-recognized and
apparently conserved feature of the asymmetric protein localization mech-
anism is interdependence among the core PCP proteins for their asymmetric
localizations (
Goodrich & Strutt, 2011
). The fully manifest asymmetric
localization of each core PCP protein depends on the intact function of each
of the other core proteins, suggesting a tight feedback-based mechanism.
Six proteins have been identified as important for establishing PCP and
whose localization satisfies these criteria. The atypical cadherin Flamingo
(Fmi) was the first protein observed in a PCP-specific asymmetric localiza-
tion, enriched on both the proximal and the distal cortices of every cell
during planar polarization of the wing (
Shimada, Usui, Yanagawa,
Takeichi, & Uemura, 2001; Usui et al., 1999
). Unipolar asymmetry was
first independently seen for the seven-pass transmembrane protein
Frizzled (Fz) (
Strutt, 2001
) and the cytosolic protein Disheveled (Dsh)
(
Axelrod, 2001
), both of which are enriched on the distal cortex of each
wing epithelial cell. This distally localized PCP complex was later found
to include Diego, another cytosolic protein with ankyrin repeats (
Das,
Jenny, Klein, Eaton, & Mlodzik, 2004
). On the opposite cell cortex, the
four-pass transmembrane protein Vang (also known as Stbm) and the
LIM-domain cytosolic protein Prickle (Pk) are enriched proximally
(
Bastock et al., 2003; Tree, Shulman, et al., 2002
). Importantly, correct
apical localization of all six of these core PCP proteins at the adherens
junction depends on the presence and function of the others. Protein
localization asymmetry builds up slowly during fly wing development,
beginning in the third instar and showing the most prominent asymmetry
during the hours just prior to the outgrowth of trichomes. After the
planar-polarized outgrowth of wing hairs, asymmetry is quickly lost.
4.2. Domineering nonautonomy: How to talk to your neighbor
Well prior to the characterization of PCP mutants in flies and the availability
of modern genetic tools to make mosaic clones, transplantation experiments
in larger insects showed that planar polarities in neighboring cells can influ-
ence each other in a non-cell-autonomous manner (
Lawrence, 1975
).
