Biomedical Engineering Reference
In-Depth Information
Including WRM-1,
C. elegans
has four
b
-catenins, one of them, SYS-1,
functions as a coactivator of POP-1 in the Wnt/
b
-catenin asymmetry path-
way (
Huang, Shetty, Robertson, & Lin, 2007; Phillips, Kidd, King, Hardin,
& Kimble, 2007
). Similar to WRM-1 and LIT-1, SYS-1 is asymmetrically
enriched in the posterior than in the anterior nuclei (
Fig. 3.1
). This SYS-1
asymmetry requires Wnt and Dishevelled proteins and suggested to be
regulated through asymmetric protein degradation, raising the possibility
that the regulation of SYS-1 is similar to that of the canonical Wnt
pathway, even though SYS-1 does not have phosphorylation sites of
GSK3
b
that is required for degradation of
b
-catenin in other species. As
the SYS-1 asymmetry does not require WRM-1 or LIT-1, the Wnt/
b
-
catenin asymmetry pathway independently regulates nuclear asymmetry
of SYS-1 and POP-1. This results in reciprocal asymmetry of POP-1 and
its coactivator SYS-1.
The reciprocal asymmetry of POP-1 and SYS-1 as well as WRM-1 ap-
pears to be counterintuitive to the observation that POP-1 binds to both
SYS-1 and WRM-1. It was recently shown that the reciprocal asymmetry
is achieved in the following way (
Fig. 3.2
)(
Yang et al., 2011
). First, bind-
ing of SYS-1 and WRM-1 is mutual inhibitory so that only free POP-1
unbound to SYS-1 but not the POP-1-SYS-1 complex binds to
WRM-1 and is exported out of nuclei. Second, phosphorylated POP-1
has a weaker affinity to WRM-1. Therefore, upon phosphorylation,
POP-1 is released from the WRM-1-LIT-1 complex, resulting in its nu-
clear export without coexport of WRM-1 and SYS-1. This mechanism
allows posterior nucleus to have mostly the POP-1-SYS-1 complex but
not free POP-1.
It was shown that the reciprocal asymmetry of nuclear POP-1 and SYS-
1 produces distinct activities of POP-1 between the daughter cells (
Kidd,
Miskowski, Siegfried, Sawa, & Kimble, 2005
). In the anterior daughter
with high POP-1 and low SYS-1, most POP-1 is free from SYS-1 and
functions as a repressor of transcription, while in the posterior daughter,
most POP-1 binds to SYS-1 and functions as a transcriptional activator.
Such difference of POP-1 functions produces distinct fates of the daughter
cells. For example, after the EMS division, POP-1 represses transcription
of the
end-1
gene that promotes endoderm formation in the anterior
MS daughter that produces mesoderm, while activating it in the posterior
E daughter that becomes endoderm (
Maduro, Lin, & Rothman, 2002;
Shetty, Lo, Robertson, & Lin, 2005
).
