Biomedical Engineering Reference
In-Depth Information
canonical Wnt/
b
-catenin signal through functional interaction with Wnt5/
Ror2 (
McKay et al., 2001; Witte et al., 2010
). Similarly, Inv and Naked both
bind to Dsh to facilitate the Wnt/PCP pathway by antagonizing Wnt/
b
-catenin signal (
Simons et al., 2005; Van Raay et al., 2007
). The
clathrin AP-2 adaptor
m
2-adaptin is associated with Dsh, and mediates
Fzd endocytosis, which is required for PCP signaling and thus for the
regulation of CE movements in
Xenopus
(
Yu et al., 2007
). This is
supported by the observation in cultured cells that interaction of Wnt5
with Fzd induces internalization of the signaling complex including Dsh
and
b
-arrestin presumably through the clathrin-mediated endocytosis
(
Chen et al., 2003
). Together with the observation that
b
-arrestin is
required for CE and mediates downstream of Dsh (
Kim & Han, 2007
),
these results suggest potential involvement of heterotrimeric G-proteins
in Wnt/PCP signaling. Consistent with this notion, the heterotrimeric
G-protein a subunit can transduce Wnt/Ca
2
รพ
signaling in zebrafish
embryos (
Slusarski et al., 1997
), and G
a
11
mediates downstream of Wnt11
and is required for CE in
Xenopus
(
Iioka et al., 2007
), and G
a
12/13
is
required for CE in zebrafish (
Lin et al., 2005
).
In addition, there are inputs at the level of other core PCP components
to regulate CE. Rack1, a Vangl2-interacting protein, is required for CE and
is capable of antagonizing Wnt/
b
-catenin signal (
Li et al., 2011
).
Being identified as a
Drosophila
homologue of misshapen, Mink1 can
bind to and phosphorylates Pk, and phosphorylated Pk is able to form a com-
plex with Vangl2 at the membrane while mediating CE in
Xenopus
(
Daulat
et al., 2012
).
It is less clear evidence for homologues of downstream mediators of
Drosophila
PCP, mediating CE in zebrafish and
Xenopus
.Abrogationof
interned
or
fuzzy
leads to only mild CE phenotypes in
Xenopus
(
Park et al.,
2006
). Consistent with this observation,
fritz
is required for only cell elonga-
tion, but not for cell polarization, of chordamesoderm cells, whereas
dsh
is
required for both processes (
Kim et al., 2010
).
There are debatable issues as to whether the Fat/Dachsous (Ds) pathway
acts in the Fz/PCP pathway or in a parallel pathway in
Drosophila
(e.g.,
Lawrence et al., 2008a
). In addition, the Fat/Ds regulates growth control
through the Hippo pathway. There is no definitive evidence that Fat/Ds acts
in the Wnt/PCP pathway in vertebrates although
fat4
genetically interacts
with
vangl2
(
Saburi et al., 2008
;
Saburi et al., 2012
).
