Biology Reference
In-Depth Information
of the basement membrane, which allows the two daughter cells to be located side-by-side.
The cleavage furrow develops not from the entire circumference of the cell, but instead
invades upwards from the basal stalk (
Figure 23.6
b). Teleologically, this can be understood
as a mechanism to ensure that both daughter cells inherit a share of the stalk and therefore
a connection with the basement membrane, but the mechanism that confines cleavage plane
initiation to the basal surface is unknown.
ORIENTATION OF THE MITOTIC SPINDLE
There are two broad ways in which correct orientation of the mitotic spindle might be
achieved: MTOCs could be aligned correctly before spindle assembly begins, or the spindle
could be allowed to form in any orientation and then brought into alignment afterwards. At
least some cell types, such as mammalian neuroepithelial cells of the cerebral cortex, provide
strong support for alignment taking place after spindle formation. In these cells, mitotic spin-
dles rotate several times before taking up their final positions
18
and, even while they are
rotating, spindles often 'stall' for a while at what will be their final orientation. This stalling
suggests that something is trying to trap the spindles on this alignment but that it only
succeeds after a few rotations have beenmade. Studies onmutants that randomize orientation
of mitotic spindles provide strong hints about the nature of the trapping mechanism. Mutants
that cause the astral microtubules to be unusually short, and therefore not to reach into the
cortical regions of the cell, cause the orientation of the spindle to be random, suggesting
that the trapping mechanism normally works by pulling the astral microtubules to specific
regions of the cortex. Mutants of budding yeast that have lost the function of the mictotubule
binding and motor protein Dynein,
19
and also mutants of the nematode Caenorhabditis elegans
that have lost the function of the Dynein-activating proteins Dnc1 and Dnc2,
20
all show
randomization of spindle orientation. Also, if a laser is used to sever the central portion of
the mitotic spindle of a one-celled embryo of C. elegans , the astral microtubules spring apart
fromeach other as if theywere being pulled towards the periphery of the cell.
21
Together, these
observations suggest a mechanism in which specific regions of the cell cortex are (especially)
able to trap astral microtubules using microtubule-binding proteins and/or to pull astral
microtubules towards them using Dynein (
Figure 23.7
). The problem of orientating mitoses
therefore becomes one of attracting astral microtubules to the correct parts of a cell.
One system in which spindle orientation has been studied extensively is single-layered
epithelium, in which the spindle is always orientated at right angles to the apico-basal
axis. There seem to be several ways in which cells can ensure this happens, different cells
apparently varying in which mechanism is of greatest importance.
Onemechanism is essentially negative, and is based on excluding asters from the apical end
of the cell. The microtubules that radiate from asters can be bound and pulled by the motor
protein Dynein, so any fixed complex that contains Dynein will tend to pull an aster toward
it as soon as a microtubule from that aster happens to make contact. At the cell cortex, Dynein
is often found in a complex with the proteins NuMA and LGN. LGN activity is repressed by
phosphorylation by the 'atypical' protein kinase (aPKC) enzymes that are located within the
apical domain of epithelial cells.
22
Active LGN/NuMA/Dynein complex is therefore
excluded from the apex of the cell, but allowed to be active elsewhere. With no Dynein pulling
