The Role of Arrestins in Development - Progress in Molecular Biology and Translational Science - page 223

regulated by Polycomb protein binding to hox promoters. 36 Zebrafish

b

arr1,

arr1, 37 shows both cytoplasmic and nuclear localization.
In the above study, it was shown that b arr1 acts as a positive replacement
factor of YY1. When

like mammalian b

arr1 interaction is lost, YY1 is preferentially localized
to the nucleus of transfected cells and zebrafish embryos where it binds to
promoter regions of cdx4 and hox factors and causes the recruitment of Pol-
ycomb repressors. As a result, the transcription of hox genes in halted and
blood development is hindered. Further studies investigating if

b

arr1 has
a general impact on Polycomb-mediated gene repression would be of high
interest. It would also be worthwhile to test whether the reported actions are
restricted to embryos of certain embryonic developmental stages or if the
described actions of

b

b

arr1 have an impact on embryonic or even adult stem

cells as well.

4.2. b arr2 in Wnt signaling
The Wnt family of secreted lipoglycoproteins represents an important class
of signaling molecules in embryonic development as well as in cancer and
aging. This family of proteins modulates cell fate by changing transcriptional
activity, cell differentiation, proliferation, migration, and polarization. Ver-
tebrate genomes encode for more than 10 different Wnt proteins, which
depend on temporal or spatial contexts trigger three different signaling sce-
narios (reviewed in Ref. 38 ). Canonical Wnt signaling functions through the
stabilization of cytosolic b -catenin that translocates to the nucleus. In the
nucleus,

-catenin activates transcription factors of the Tcf/Lef family. 39
Noncanonical Wnt pathways, on the other hand, do not rely on

b

-catenin.
These can be further subdivided into two cascades. Noncanonical Wnt
stimulation through the calcium pathway leads to the release of intracellular
calcium ions. This in turn activates calcium-calmodulin-dependent kinase
II, protein kinase C, or calcineurin. 40 The second noncanonical cascade acts
through the activation of the small G proteins RhoA and Rac. Subsequent
activation of RhoA kinase and JNK results in cytoskeletal rearrangement. 41
The latter pathway is also referred to the planar cell polarity (PCP) pathway,
as it regulates the polarization of cells with respect to the anterior-posterior
embryonic axis and results in the so-called convergent extension movements
that are indispensable for axis elongation. 42 All three Wnt pathways are
transduced by Frizzled proteins, which were first identified in Drosophila
more than 20 years ago. 43 Frizzleds are seven transmembrane spanning pro-
teins that have been considered as GPCR-like molecules. 44-47 Studies using
G protein inhibitors in zebrafish embryos as well as experiments in cultured

b