Biomedical Engineering Reference
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mediated by Disheveled and Van Gogh. In addition, Frizzled and Dishev-
eled are localized on the distal membrane of fly wing epithelial cells and Van
Gogh and Prickle are localized on the proximal membrane shortly before the
appearance of morphological asymmetry along the proximal-distal axis. It is
possible that Van Gogh may be activated on the proximal membrane only
and therefore Frizzled is removed from the cell surface on the proximal
membrane. It is also possible that Disheveled is highly activated on the distal
membrane such that it is able to keep Frizzled on the plasma membrane.
Vangl2 itself undergoes complex phosphorylation as well (
Gao et al.,
2011
), which may represent an input of another regulatory signal. However,
it is currently unknown whether Frizzled3 hyperphosphrylation induced by
Disheveled inhibits endocytosis or promotes exocytosis. Both cases are
consistent with the current findings, and determining which case is true will
certainly shed more light on PCP signaling.
6. LOCALIZATION OF VANGL2 PUNCTA ON
FILOPODIA TIPS SUGGESTS THAT PCP SIGNALING
MAY STEER GROWTH CONES
In live growth cones, Vangl2 protein is highly enriched on the tips of
extending filopodia but not the shrinking filopodia. This suggests that at least
one aspect of PCP-like signaling is selectively activated on those filopodia
tips and not in the rest of the growth cones, which is inactivated by Dishev-
eled1 (
Shafer et al., 2011
)(
Fig. 6.3C
). In other words, the asymmetry in
growth cones may be manifested by differences among filopodia, the ones
with Vangl2 versus those without. This opens up the opportunity to under-
stand how PCP signaling takes place in growth cones. First, this provides a
clue that the filopodia tips, not the entire filopodia, are sensors of the growth
cone; second, this also suggests that Frizzled3, whose phosphorylation is
reduced by Vangl2, may be endocytosed from the tips, carrying signal into
the growth cone. It will be very informative to follow Frizzled3 trafficking
and decipher the information Frizzled3 may bring into the growth cone. On
the other hand, following the question on how Vangl2 is localized to the
tips can potentially lead to the answers of how upstream activators of
PCP signaling regulate polarity.
In a previous study, aPKC/Par3/Par6 complex, a key component of the
A-BP signaling, was found to mediate Wnt attraction during anterior turn-
ing of commissural axons (
Wolf et al., 2008
). There has been evidence that
A-BP and PCP signaling pathways interact with each other intimately. First,
