Guidance by Chemotaxis - Mechanisms of Morphogenesis - page 101

FIGURE 9.8 Signalling pathways responsible for separating zones of protrusion from zones of myosin II
contraction.
The dynamics of cGMP in the time domain suggest the possibility of error-checking nega-
tive feedback. As was mentioned above, cGMP concentrations reflect the rate of change of
external cAMP and are stable only when the absolute concentration of cAMP is increasing.
As long as a cell is migrating up a cAMP gradient, this concentration will be increasing,
cGMP will be stable, and the leading edge will have no rivals trying to pull the cell another
way. If the concentration of external cAMP ceases to increase, though d either because the
cell has made an error and is migrating across or even down the gradient, or because the
source has moved d internal levels of cGMP will fall and lateral domains of the membrane
will be allowed to begin protrusive exploration. Those facing up the new gradient will be
most likely to organize themselves into a new leading edge, and the cell will set off in
another direction. Cells tend to support only one leading edge for more than a few seconds,
and the leading edge most favoured by the external gradient 'wins'. 28 Indeed, in shallow
gradients the rate of leading edge production is almost independent of the gradient, and
the gradient simply biases which ones persist. 29 Cell turning by decay of the original leading
edge and protrusion of a new one has been directly observed in D. discoideum, 30 although
less abrupt turning of the whole cell, so that the existing leading edge continues to lead,
can also be seen.
In the absence of external cues, cells of D. discoideum continue to move. When they have
plenty of food, they move randomly (which makes sense teleologically, because it will opti-
mize their ability to reach and engulf bacteria in an area that must be rich in them for the
amoebae to be replete). Starving cells also move, but these maintain their original direction
for many minutes. This period, the 'persistence time of movement', is much longer than
the survival time of an individual leading edge projection (pseudopodium). Again, it makes
sense teleologically speaking, because the amoeba has no reason to spend time in an area
devoid of food and it needs to move a long way away in the hope of finding richer pickings.
Starving increases cGMP concentrations and suppresses production of leading edges from