Biomedical Engineering Reference
In-Depth Information
relationship to one another. One such pathway is referred to as the Fat/
Dachsous (Ds) pathway (
Thomas & Strutt, 2012
). Fat and Dachsous are
atypical cadherins that interact heterotypically between adjacent cells
(
Matakatsu & Blair, 2004
). Members of the Fat/Ds group show signs of sub-
cellular localization (
Ambegaonkar, Pan, Mani, Feng, & Irvine, 2012;
Bosveld et al., 2012; Brittle, Thomas, & Strutt, 2012
). The Fat and
Dachsous proteins are enriched on one side or the other. Although the
subcellular localization is not as strict as is seen for other PCP
determinants (see below), its strength is reinforced by Fat/Ds intercellular
dimerization as well as processes that regulate the activity of these two
proteins (
Ambegaonkar et al., 2012; Brittle et al., 2012
).
Four-jointed (Fj) is a Golgi-associated kinase that phosphorylates the extra-
cellular domain of Fat andDs (
Simon, Xu, Ishikawa, & Irvine, 2010
). Phosphor-
ylation of Fat by Fj increases its affinity for Ds, while phosphorylation of Ds
decreases its affinity for Fat (
Brittle, Repiso, Casal, Lawrence, & Strutt, 2010;
Simon et al., 2010
). In many tissues, Fj is expressed in a graded pattern, which
results in graded activity of Fat and Ds (
Simon, 2004
). The net result of the
action of Fj and the polarized distribution of Fat and Ds is that, although the
proteins may be distributed throughout the cell, the active forms will
segregate to opposite sides. In this way, the proteins establish PCP. Although
there are some exceptions, neither does the polarization of active Fat and Ds
require the activity of the core determinants (see below) nor does the Fat/Ds
pathway affect core protein localization in individual cells (it does affect global
polarization) (
Casal, Lawrence, & Struhl, 2006
). Thus, it appears that for the
most part the Fat/Ds and core pathways act in parallel to each other rather
than in a simple linear pathway (
Lawrence, Struhl, & Casal, 2007
).
2.2. The core pathway
A second major pathway identified in Drosophila is referred to as the “core”
pathway (
Gray, Roszko, & Solnica-Krezel, 2011; Maung & Jenny, 2011
).
It is composed of the seven-pass transmembrane receptor Frizzled (Fz),
the cytoplasmic PDZ domain-containing protein Disheveled (Dsh), the
atypical cadherin Flamingo/Starry night (Fmi/Stan), the tetramembrane-
spanning protein Van gogh/strabismus (Vang/Stbm), the Lim and Pet
domain-containing cytoplasmic protein Prickle (Pk), and the ankyrin
domain-containing protein Diego (Dgo).
Although PCP affects polarity over an entire tissue, it is established at the
level of
individual cells. Within a cell, PCP results in the polarized
