Guidance by Chemotaxis - Mechanisms of Morphogenesis - page 102

FIGURE 9.9 Persistence of movement by D. discoideum amoebae free of chemotactic cues, achieved by
a left e right alternation of the production of new leading edges ('pseudopodia' in amoebae).

the training end of the cell. That is one mechanism for persistence. The other seems to be
achieved by a default mechanism that consists of a new projection forming to one side of
an existing one, usually at around 55 degrees to it, then a new one forming to the side of
that, and so on ( Figure 9.9 ). Critically, the cell maintains a sequence of alternating these
new projections left and right, so that on average it persists in its original direction. 10

HOW GOOD A MODEL IS D. DISCOIDEUM FOR OTHER SPECIES?

D. discoideum has been chosen as a model to illustrate the principles of chemotaxis simply
because it is the system that is understood in most detail. The complexity of metazoan devel-
opment makes detailed analysis of the cellular mechanisms of chemotaxis difficult in the
context of an embryo. Some chemotactic cells of adults, such as neutrophil polymorphonu-
clear leukocytes of the mammalian immune system, can be obtained in large enough quan-
tities for their chemotactic mechanisms to be studied in detail so that they can be compared
with those of D. discoideum.
Neutrophils migrate chemotactically towards N-formyl peptides such as fMet-Leu-Phe,
which are produced by bacteria at sites of infection, and will show robust responses to
such chemoattractants in simple culture systems. Migrating neutrophils have a general
form similar to myxamoebae, having a leading edge full of a fine network of actin (where
protrusion is concentrated) and a myosin-rich trailing edge. When presented with a shallow
external gradient of chemoattractant, neutrophils generate a steep gradient of internal
PI(3,4,5)P 3 , which can be demonstrated by tagging the PI(3,4,5)P 3 -seeking PH domain of
Akt. 31 Furthermore, experiments with inhibitors confirm that production of PI(3,4,5)P 3 is
necessary for chemotaxis. 32 As in myxamoebae, PI(3,4,5)P 3 production leads to activation
of Rac 33 and thence production of a protrusive network of actin. Direct local application
of a membrane-permeable complex of PI(3,4,5)P 3 to fibroblasts, even in the absence of an
external gradient of chemoattractant, triggers polarization of the cell and chemotactic move-
ment. 34 All of this suggests that the chemotaxis of neutrophils is remarkably similar to that
of myxamoebae. There are some differences, however. Neutrophils seem not to segregate
PTEN to their sides and trailing edges and rely completely on myosin to prevent lateral
protrusion. The pathway that controls myosin II via Rho is quite separate from that