Researchers take a closer look at the subtle ways that cells usefor signaling
THE building of a multiccllular organism
requires an intricate network of signals
going to and fro between the cells that
constitute the organism. Traditionally,
these signals are studied in terms of the
effects they cause, in terms of their
molecular constitution and in the
manner in which they are sensed. The
entire approach presupposes that the
important questions concern only
signal, receptor and intracellular
changes that occur as a consequence of
the signal binding to its receptor.
However, as we know all too well
from our experience of the most com-
mon form of communication between
human beings, speech, a crucial aspect
of signalling has to do with how the
signal varies in time. To take a simple
example: depending on how it is modu-
lated, the same set of sounds can convey
a question or an answer. Unfortunately,
temporal patterning in multicellular
signalling is a relatively unexplored sub-
ject. One reason for this neglect is that it
is not an easy matter to measure rapid
variations in the concentration of a
chemical that may be present in very
tiny amounts to begin with. Another is
that most biologists prefer to spend
their time on the molecular basis of signalling, which is a more glamorous area
than signal patterning.
Cornelis I Weijer and his colleagues
at the University of Dundee, UK, are
one exception to this rule. Weijer has
taken advantages of the several attractive features found in the amoebae
Diciyostelium discoideum to study the
fine details of temporal signalling
between cells. In this he has been aided
by two factors. One, Diclyosteliurn
amoebae interact with each other by
means of clock-like periodic signals of a
known chemical, cyclic Amp. Two, cells
respond to an external source of cyclic
AMP by moving towards the source and
simultaneously relaying the signal.
Because of the relay, waves of cyclic
AMP travel outwards from a source. And
due to this movement response, the
outwardly propaAating waves of cyclic
AMP elicit inwardly travelling waves of
cellular motion that cause amoebae to
aggregate. The entire process can easily
be photographed and analysed in a
video apparatus. The speeds involved
are small, of the order of one-hundredth
to one-tenth of a millimetre per minute
and the period between two signals is
large, about five minutes, so the phenomenon needs to be artificially speeded up during photography (Developmental Biology, Vol 181).
Weher's latest observations show
just how subtle the effects of altered signalling can be. 'the object of the study is a mutant named G45v, that is believed to
remain in a permanently sensitive state
to the cyclic AMP signal (in contrast to
the normal, parental, strain that gets
temporarily desensitised after receiving a
signal). Weijer and colleagues report
that the aggregation process is deranged
in the mutant. In the parental strain, the
outwardly travelling Waves Of Cyclic AMP
that initiate aggregation get transformed
to screw-shaped waves. These also start
from the centre, which now adopts a
nipplc-like form at its tip after the aggregation is completed. The screw waves
direct extensive rotational and upwarddirected movement of amoebae up the
axis of the slug. One consequence is a
clear spatial segregation of the two cell
types that go on to shape the terminally
differentiated stage of the lific,cycle of
Diciyostelium.
In G45v, everything appears to procced as usual until the end of aggregation. After that, instead of a screwshaped upwardly moving wave of cellular movement, what one
finds is a series of waves
going round and round
the centre in a circular
fashion. As this happens,
a dip appears in the
centre of the aggregate,
which gradually disappears altogether and
causes the aggregate to
take on a ring-like
appearance. 'I he ring
finally breaks up into a
number of small, terminally differentiated
structures instead of one
large structure as usual.
The ultimate (meaning,
evolutionary) consequence of the mutation
appears to be a reduction in the overall size
of the final stage.
Correlated with aberrant
wave propagation and probably causally related to it - the
spatial segregation of cell types that is
normally a corollary of the appearance
ol'the nipple-shaped tip, fails to occur.
The most important implication of
this study is that the defect, which can
have a subtle but an important effect in
the signalling machinery would never
have been perceived if one had struck to
the measuring techniques of conventional biochemistry. What still remains
to be done, however, is to establish a definite link between the immediate consequence of the mutation at the molecular
level and altered signal dynamics.
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