Insall R. Dispatch. Dictyostelium chemotaxis: fascism through the back door? Curr Biol. 2003 Apr 29;13(9):R353-4. doi: 10.1016/s0960-9822(03)00274-4. PMID: 12725750.
Abstract
Aggregating Dictyostelium cells secrete cyclic AMP to attract their neighbours by chemotaxis. It has now been shown that adenylyl cyclase is enriched in the rear of cells, and this localisation is required for normal aggregation.
Dictyostelium discoideum cells undergo a major lifestyle change when they get hungry. They grow as unicellular amoebas, but when food starts to get short they aggregate into masses of up to a million cells, which in turn differentiate and sort out into mushroom-shaped fruiting bodies. Aggregation and differentiation are rigorously controlled by a multitude of signalling pathways, which together cause cells to behave with amazing synchrony. Sydney Brenner is said to have remarked “Good God! Molecular Fascism!” on seeing thousands of aggregates simultaneously forming fruiting bodies [1]. Cell behaviour is regulated just as tightly during aggregation. Every few minutes, waves of movement propagate outwards from random centres. As the front of a wave passes, the cells in its vicinity lurch towards the source of the wave. Each wave thus pulls every cell it passes towards the centre, providing a simple mechanism to coordinate aggregation; the process is so efficient that only a few tens of waves are needed to convert a homogenous lawn of cells into discrete aggregates of as many as 106 cells.
In Dictyostelium, the waves of movement are choreographed by cyclic AMP (cAMP). One cell at the centre emits a pulse of cAMP. Cells that receive a cAMP signal also emit cAMP themselves, which reinforces the signal and can allow a single wave to persist for several centimetres. The surrounding cells move by chemotaxis towards the source of the cAMP, generating the wave of movement. This highly sensitive, synchronized chemotaxis is a boon for experimental work – aggregating Dictyostelium cells are essentially specialized cAMP chemotaxis machines, which has lately made Dictyostelium the favourite organism of the chemotaxis field.
About halfway through the process of aggregation, the cells’ behaviour alters – they elongate, join up end to end and form thick streams which allow yet more rapid and well-coordinated movement. Most researchers have hitherto believed that this behaviour is controlled by specialised cell–cell adhesions, but a recent study [2] suggests a new view. Kriebel et al.[2] have shown that adenylyl cyclase A (ACA), the enzyme which makes the cAMP used in aggregation, is enriched at the rear of polarized cells. This implies that the cAMP signals in streaming cells are far more spatially defined than previously thought. It appears that streaming cells are not responding to broad cAMP waves sweeping past them, as they see early in aggregation, but rather to a localised signal from the posterior end of the cell in front.
These localised signals cannot be shown directly, unlike the earlier, broader cAMP waves, which were revealed in a gorgeous experiment using isotope dilution some years ago [3]. As well as being built on a very small scale, the localised signals are extremely short lived, as cells secrete large amounts of a very active phosphodiesterase [4]. Kriebel et al.[2], however, have demonstrated their presence in several ways. The clearest was by following chemotaxis in ACA null mutants. Lack of ACA does not seem to affect cells’ ability to do chemotaxis, but it does change the pattern: if a microneedle full of cAMP is held near a plate of ACA null cells, they all orient towards the stimulus (Figure 1). Wild-type cells are more subtle: they orient in a curved, fan-shaped pattern, with more distant cells pointing towards other cells nearer the needle, rather than the needle itself (Figure 1). Presumably in streams, where the cell density is far greater, each cell’s responses are almost exclusively towards the rear part of the cell in front. In other words, streaming cells are not armies marching to the decree of a few molecular fascists, but more like a long line of dogs sniffing one another’s bottoms as they walk in the park (as a crude scientist remarked at a recent meeting).
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Figure 1 Wild type (left panel) and adenylyl cyclase A mutants (aca− cells, right panel) moving by chemotaxis towards a microneedle containing 1 μM cAMP. Wild-type cells form streams, while aca− cells orient individually towards the needle. (Images courtesy of Paul Kriebel and Carole Parent.)
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