Biomedical Engineering Reference
In-Depth Information
Disheveled 2 can recruit
b
-arrestin 2 to trigger Frizzled4 endocytosis upon
Wnt5a stimulation (
Chen et al., 2003
). In addition, gain- and loss-
of-function studies of
b
-arrestin 2 in
Xenopus
show that its endocytic
activity is essential for proper CE movements without affecting cell-fate
determination, suggesting the essential role of endocytosis in regulating
PCP (
Kim & Han, 2007
). By
in vivo
time-lapse imaging on
Drosophila
wing, Uemura's group observed that Frizzled- and Flamingo-containing
intracellular particles preferentially move toward distal cell boundaries
along P-D-oriented microtubules prior to prehair formation (
Shimada,
Yonemura, Ohkura, Strutt, & Uemura, 2006
). Therefore, polarized
vesicular trafficking of Frizzled proteins was proposed to be one of
the possible mechanisms underlying PCP establishment (
Gagliardi,
Piddini, & Vincent, 2008
). Recently, there is more evidence to
indicate that endocytosis is essential for PCP establishment. Rab4-
and Rab11-mediated Frizzled recycling favors PCP over canonical Wnt
signaling (
Purvanov, Koval, & Katanaev, 2010
). In addition, a Rab5
effector, Rabenosyn-5 (Rbsn-5), is required for PCP in the fly wing
epithelia cells through regulating endocytic trafficking of Flamingo
(
Mottola, Classen, Gonzalez-Gaitan, Eaton, & Zerial, 2010
). In the
Drosophila
eye, internalization of Flamingo requires AP-2 bound Echinoid
(Ed), an adherens junction-associated cell adhesion molecule.
Ed
mutant
exhibited more Flamingo proteins on the membrane of nonrotating
interommatidial cells resulting in misorientation of neighboring
photoreceptors in ommatidia (
Ho et al., 2010
). Apart from core PCP
proteins, Syndecan 4-mediated R-spondin 3 signal can induce Wnt/PCP
through clathrin-mediated endocytosis (
Ohkawara, Glinka, & Niehrs,
2011
). Furthermore, Wnt11 controls mesendodermal cell cohesion and
migration in zebrafish gastrulation through regulating Rab5-mediated
endocytosis of E-cadherin (
Ulrich et al., 2005
). In another report, Ryk is
found to act as a coreceptor of Frizzled 7 to promote Wnt11-stimulated
endocytosis of Disheveled in
Xenopus
CE movements (
Kim, Her, & Han,
2008
). Together, endocytosis of core PCP proteins, especially Frizzleds,
plays a key role in establishing PCP and Wnt proteins may control
PCP-like processes through regulating endocytosis. However, how
Wnts regulate endocytosis and how endocytosis leads to asymmetrically
localized core PCP protein still remain to be elucidated. Interestingly, a
recent paper suggested a correlation between Frizzled 3 phosphorylation
and its endocytosis, although whether Wnt proteins regulate
phosphorylation of Frizzled 3 is unknown (
Shafer et al., 2011
). It will be
