Biology Reference
In-Depth Information
FIGURE 23.7
A model for orientation of the mitotic spindle through trapping by the cortical cytoplasm.
asters to the apex while there is active Dynein in other parts of the cell, no aster is likely to
remain in the cells' apex for long. With this system, the spindle is therefore likely to form in
any orientation except one that runs up and down the cell, along the apico-basal axis.
The presence of adherens junctions in a band located mainly just below the apical domain,
where the lateral domain begins, can provide a positive orientating influence. In the ecto-
derm epithelium of D. melanogaster, cell divisions are normally orientated so that the cleavage
plane is perpendicular to the basement membrane and each daughter cell therefore main-
tains contact with it. If formation of adherens junctions is disrupted by transfecting embryos
with interfering RNA that targets junctional components, the normal orientation is lost. The
position of the mitotic spindle in normal epithelial cells is such that its poles are close to adhe-
rens junctions, suggesting that there may possibly be a direct interaction between the two.
This possibility is supported by the fact that the inner face of adherens junctions contains
a large number of proteins, amongst which are some that can bind microtubules. For
example, the protein APC is a component of adherens junctions that binds the junctional
protein
-catenin and the microtubule-binding protein EB1. APC/EB1 complexes bind and
stabilize microtubules.
23
Mutation of either APC or EB1 causes the same loss of orientation
control as loss of the junctions themselves, supporting the idea that the adherens-APC-
EB1-spindle link is real and important in drawing asters towards the junctional belt
(
Figure 23.8
). There is also evidence from other systems that
b
-catenin can bind Dynein,
24
and this may also act to keep astral microtubules in the region of adherens junctions.
This adhesion-dependent system controls spindle orientation in other cell types too. In the
testis of D. melanogaster, there are stem cells that maintain their own numbers and give rise to
daughter cells that will eventually produce sperm. The stem cells bind to a central conden-
sate of somatic cells called the 'hub'. Adhesion between stem cells and the hub is mediated at
least in part by E-cadherin, which forms adherens junction-like complexes that include APC
on their inner faces. Normally, the mitotic spindle of a dividing germ cell is orientated so that
one pole is near the adhesion site; this will leave one daughter cell still contacting the hub
directly and the other not (
Figure 23.9
). The daughter still in contact with the hub retains
b
