Classifying chemoreceptors: quantity versus quality

Classifying chemoreceptors: quantity versus quality

This issue of The EMBO Journal features significant novel insight into bacterial chemotaxis. Work from the Sourjik lab reveals that chemoeffectors should be grouped into direct or indirect receptor binders. They also report that distinct functional properties associate with this binding mechanism.

EMBO J 29 20, 3484–3495 (2010); published online September102010

Advances in genomic and proteomic methods provide the means to ascertain not only what receptors are present in a given cell but also how prevalent they are. While it is reasonable to assume that receptor concentration has a critical role in cell physiology, a new study published in this issue of The EMBO Journal suggests that the more relevant parameter can be a receptor's molecular mechanism. The findings arose from studies focused on bacterial chemotaxis. Chemotactic bacteria sense their chemical environment through a battery of transmembrane chemoreceptors. Previously, these receptors were grouped into two categories: high and low abundance. Neumann et al (2010) postulated that an alternative classification might be more apt. They note that chemoeffectors can bind their chemoreceptor either directly or indirectly through a periplasmic-binding protein (BP) intermediary, and they provide evidence that these distinct sensing mechanisms have different properties: indirect binding offers the opportunity to control sensitivity while direct binding gives responses over a wider concentration range. These different sensing mechanisms may be exploited by bacteria to survive in diverse niches.

Bacteria can pursue favourable niches through chemotaxis—they bias their swimming behaviour in response to their extracellular environment. The bacterial chemotaxis-signalling system has emerged as a paradigm for transmembrane signalling and molecular information processing (Hazelbauer et al, 2008; Sourjik and Armitage, 2010). The system has been studied extensively in Escherichia coli, the signalling components are known, and their general roles have been elucidated. Indeed, we are poised to understand this bacterial system from the level of atomic interactions to emergent decision-making behaviour. Nevertheless, features of the chemotaxis system remain paradoxical. Chemotaxis signalling is surprisingly economical yet capable of exquisite sensory performance. Chemotactic E. coli can both respond and adapt to stimuli using a collection of chemoreceptors and only six other gene products. This apparent simplicity belies impressive sensory performance. For instance, the system can respond to as few as 10 molecules of chemoreceptor-bound ligand and adapt precisely to chemoeffector concentrations spanning 4–5 orders of magnitude (Mesibov et al, 1973; Segall et al, 1986). Moreover, in complex environments, the chemotaxis system integrates and reconciles diverse, contradictory stimuli (Figure 1).

Figure 1.

In a physiological niche, bacteria encounter diverse chemotactic signals that influence their behaviour. Chemotaxis signalling is mediated by a collection of transmembrane chemoreceptors. E. coli possess chemoreceptors (light blue) that can bind ligand directly, as well as those that (green) sense ligand indirectly via binding proteins (brown). Signalling responses from both classes are amplified and integrated in an inter-connected array of mixed chemoreceptors and downstream signalling components.

The sophisticated sensory performance arises from the inter-connectivity of the chemoreceptors (Bray et al, 1998). Chemotaxis signalling is amplified, tuned, and integrated by communication between coupled teams of chemoreceptors (Ames et al, 2002; Gestwicki and Kiessling, 2002; Sourjik and Berg, 2004; Mello and Tu, 2005). In E. coli, these signalling teams are composed of receptor combinations that can respond to a unique set ligands. Responses are elicited either via direct binding to the chemoreceptor (e.g. Tsr, Tar) or through an intermediary periplasmic-BP (Tap, Trg) (Figure 1). Earlier estimates of chemoreceptor concentrations identified the direct-binding receptors as major and those chemoreceptors that act in conjunction with BPs as minor. Interestingly, the BPs also shuttle their chemoeffector ligands to the ATP-binding cassette transporters responsible for nutrient uptake. The apparent link between the indirectly signalling chemoreceptors and the nutrient uptake system inspired Sourjik and Berg (2004) to reexamine the oft-overlooked BP-dependent chemoreceptors. Their study notes that the concentration of the ‘minor' receptors depends upon growth conditions. Moreover, a comparison of sensing by direct and indirect chemoeffector interaction reveals that each molecular mechanism for signal recognition has a significant effect on signal sensitivity, integration, and response range.

Sourjik and Berg (2004) used a FRET assay to monitor the signalling responses of both classes of chemoreceptor in live bacteria. The authors determined signal strength and dynamic response range for attractants sensed either directly (serine or aspartate) or indirectly (galactose, ribose, or Pro-Leu dipeptide). Consistent with previous reports, bacteria managed to respond and adapt to directly sensed ligands at ambient concentrations ranging from 4 to 5 orders of magnitude (Mesibov et al, 1973). In contrast, ligands sensed by the BP intermediaries elicited responses over a narrower concentration regime; the dynamic sensitivity range for the indirectly sensed ligands was limited to 2 to 3 orders of magnitude. What could account for the discrepancy? When normalized to their relative representation in signalling teams, the minor chemoreceptors signalled just as potently as their major peers. The authors conclude that the minor, indirect chemoreceptors are constrained by the expression levels of the BP. Chemoreceptors that sense ligands directly are responsive to the intracellular adaptation mechanisms that dampen responses. The BPs, however, do not adapt directly and remain susceptible to ligand saturation. Thus, for cells to tune responses to signals that act indirectly, they must change their BP production level.

If direct ligand-binding confers such an expansive response range, why deploy BPs as signalling intermediaries? The authors propose an intriguing evolutionary possibility. The BPs serve dual roles as both chemotaxis receptors and nutrient transporters. Navigating to nutrient-dense niches is profitable only to the extent that the bacterium can absorb and use the resources. By coupling chemosensing and uptake through BP intermediaries, bacteria pursue transported nutrients until their ability to import them is saturated. Beyond saturation, the cell is free to pursue alternative resources sensed by the more widely responsive direct-binding chemoreceptors. In the meantime, expression of BPs and metabolic systems can be upregulated to concomitantly pursue and capitalize on the nutrient resources. In this way, indirect ligand sensing may be another deceptively simple, functionally sophisticated chemotaxis optimization that couples motility with nutrient utilization.