Biomedical Engineering Reference
In-Depth Information
aPKC can inhibit Frizzled/PCP signaling by directly phosphorylating the
intracellular domain of Frizzled (
Djiane, Yogev, & Mlodzik, 2005
); second,
Disheveled directly binds to Lgl, a substrate of aPKC, and regulates the
localization of Lgl (
Dollar, Weber, Mlodzik, & Sokol, 2005
). Therefore,
there may exist a connection that integrates these two polarity signaling
pathways in epithelial cells and in axonal growth cones. It is now possible
to study the mechanisms of how A-BP signaling components may interact
with PCP components in commissural axon growth cones. How, for exam-
ple, does aPKC affect Frizzled3 phosphorylation and trafficking will provide
clues to how signaling events take place in growth cones. Understanding
what effect these signaling events have on cytoskeletal structures (the micro-
tubules and the actin system) during growth cone turning will eventually
solve this century-old mystery of axon guidance.
Growth cones are also repelled byWnts via a different receptor Ryk (
Keeble
et al., 2006; Liu et al., 2005
). Ryk signaling is still relatively unclear although it is
thought to involve the src family kinases in
Drosophila
(
Wouda, Bansraj, de Jong,
Noordermeer, & Fradkin, 2008
). In vertebrate, the Wnt/Calcium signaling has
been implicated in Ryk signaling (
Hutchins et al., 2011; Li et al., 2009; Li,
Hutchins, & Kalil, 2010
). The relationship of Ryk with PCP signaling
components has been unknown. However, a recent study suggests that Ryk
signaling may converge with Frizzled/PCP via interacting with Vangl2
(
Macheda et al., 2012
). This raises the interesting question whether a
common core mechanism causes both attraction and repulsion or whether
attraction and repulsion are mediated by totally different mechanisms. The
remarkable observation that growth cone attraction and repulsion can be
switched by the ratio of cAMP and cGMP suggests a common core may
exist (
Song et al., 1998; Song, Ming, & Poo, 1997
).
7. ARE THERE GROWTH CONE
GROWTH CONE
INTERACTIONS DURING PCP-MEDIATED TURNING?
-
Cell-cell interaction is an essential component in PCP signaling. Sev-
eral PCP components have both cell-autonomous and cell-nonautonomous
functions. If PCP signaling module functions in the growth cones, are there
any similar cell-cell interactions?
Neurons of the same type are often born at the same time and have sim-
ilar time course in their developmental program. Neurons and axons cer-
tainly have the opportunities to interact with each other during
pathfinding. In the spinal cord, commissural neurons that are born at the
