Biomedical Engineering Reference
In-Depth Information
2. CONNECTING CELL CORTEX TO NUCLEI
At telophase of divisions when two daughter nuclei are formed,
WRM-1 localized preferentially to the posterior than anterior nuclei
(
Fig. 3.1
C) (
Takeshita & Sawa, 2005; Nakamura et al., 2005
). This is in
good contrast to its anterior cortical localization that is still observed
during telophase. Photobleaching experiments revealed that WRM-1 in
the anterior cytoplasm and nucleus as well as that in the posterior side
accumulates in the posterior nucleus and that the nuclear export rates of
WRM-1 are higher in the anterior nucleus. This nuclear asymmetry of
WRM-1 is regulated by WRM-1 itself on the anterior cortex, as
expression of WRM-1::CAAX that uniformly localized to the cortex
inhibits WRM-1 localization in both nuclei (
Mizumoto & Sawa, 2007a
).
Cortical WRM-1 recruits APR-1 to the anterior cortex. In
apr-1
mutants, WRM-1 nuclear export is inhibited, resulting in its localization
in both nuclei. Thus, APR-1 on the cortex mediates the effects of
WRM-1 in the inhibition of WRM-1 nuclear localization.
In other organisms, it is well known that APC functions in the degrad-
ation of
b
-catenin (
Cadigan & Peifer, 2009; MacDonald, Tamai, & He,
2009
). However, in asymmetric cell division in
C. elegans
, levels of
WRM-1/
b
-catenin are not affected in
apr-1
mutants. APC is also known
to stabilize microtubules by binding to their plus ends in mammalian cells
(
Dikovskaya, Zumbrunn, Penman, & N¨thke, 2001
). Although this
function of APC has not been shown to regulate
b
-catenin, we have
recently showed that APC regulates
b
-catenin nuclear localization
through microtubules in the EMS blastomere (
Sugioka et al., 2011
).
APR-1 on the anterior cortex stabilizes astral microtubules, creating
asymmetry of spindle (more astral microtubules from the anterior spindle
pole than from the posterior one) (
Fig. 3.1
C). Disruption of this
spindle asymmetry by laser irradiation of the anterior spindle pole
disrupted nuclear asymmetry of WRM-1, while the enhancement of the
spindle asymmetry by the posterior irradiation caused concomitant
increase of WRM-1 nuclear asymmetry. Further, the posterior irradiation
in
mom-2
/Wnt mutants in which asymmetry of spindle and nuclear
WRM-1 is disrupted rescued asymmetric POP-1/TCF localization (see
below) regulated by nuclear WRM-1. These results showed that spindle
microtubules stabilized by APR-1 enhance export of WRM-1 from the
anterior nucleus, creating its nuclear asymmetry. How spindle regulates
