Biology Reference
In-Depth Information
organization is lost, the cortex is able to accommodate protrusive actin. Mutant D. discoideum
that have no functional myosin II cannot produce myosin filaments; they form lateral
pseudopodia that can change the direction of cell movement and confuse chemotaxis
23
(
Figure 9.7
). Conversely, experimentally driven increase in the cytoplasmic levels of cGMP
increases the speed of chemotaxis through reduced 'wasted' protrusion in the lateral parts
of the cell.
21
The efficiency of cGMP-driven myosin activation is useful for preventing lateral
extension, but would be disasterous if it were allowed to convert even the leading edge cyto-
skeleton to acin/myosin bundles. This is prevented by another kinase, myosin heavy chain
kinase A (MHCK-A) which locates to the leading edge because it can bind to the fine fila-
ments of F-actin that dominate that area.
24
e
26
MHCK-A phosphorylates myosin II heavy
chains in a manner that prevents them from forming filaments, even when the cGMP
pathway is active. The leading edge is therefore 'safe'.
The cGMP signalling system is at the heart of a feedback system that operates in both the
space and time domains. The spatial function ensures that, in a cell migrating up a chemo-
tactic gradient, protrusive activity is confined to the leading edge. The fine actin filaments
already present there recruit MHCK-A to protect the area from formation of myosin II fila-
ments, but all other parts of the cell are encouraged by cGMP to form myosin II filaments
and are therefore prevented from producing new protrusions of their own. Assuming that
the cGMP is produced mainly at the leading edge, this system would allow an established
leading edge to hold back any potential rivals, and is an example of lateral inhibition
(
Figure 9.8
).
The importance of mutual antagonism between the domains of the cell full of protrusive
actin and those full of myosin filaments has been demonstrated dramatically in small frag-
ments of fish keratinocytes
d
highly mobile cells that are unusually large and accessible.
When the cells are divided into fragments, some are inherently polarized and some are not
because their cytoskeletons are more or less homogenous. If a transient mechanical stimulus
is applied to one part of an unpolarized cell fragment, the cytoskeleton responds by organ-
izing myosin locally to resist deformation of the cytoskeleton (Chapter 5). Remarkably, this
induced anisotropy then polarizes the cell so that a leading edge forms, and the cell begins
to move; it then retains its polarity even in the absence of the pressure that caused it.
27
Once their symmetry is broken, cells can therefore set up a polarized locomotion system by
adaptive self-organization.
FIGURE 9.7
The role of myosin II filaments in suppressing formation of lateral pseudopodia.
