Decoding the chemotactic signal

Abstract

From an individual bacterium to the cells that compose the human immune system, cellular chemotaxis plays a fundamental role in allowing cells to navigate, interpret, and respond to their environments. While many features of cellular chemotaxis are shared among systems as diverse as bacteria and human immune cells, the machinery that guides the migration of these model organisms varies widely. In this article, we review current literature on the diversity of chemoattractant ligands, the cell surface receptors that detect and process chemotactic gradients, and the link between signal recognition and the regulation of cellular machinery that allow for efficient directed cellular movement. These facets of cellular chemotaxis are compared among E. coli, Dictyostelium discoideum, and mammalian neutrophils to derive organizational principles by which diverse cell systems sense and respond to chemotactic gradients to initiate cellular migration.

Keywords: G protein-coupled receptor; chemotaxis; communication theory; methyl-accepting chemotaxis protein receptor.

Figure 1

A communication model for cellular chemotaxis in prokaryotic and eukaryotic systems. (A) The Shannon‐Weaver model of communication. The input of the prokaryotic (B) and eukaryotic (C) chemotactic communication system can be considered the interaction of the message (i.e., chemoeffector) and the transmitter (i.e., chemoattractant receptor). The input is transmitted over a noisy channel (i.e., intracellular signaling cascades) to a receiver which decodes and reproduces the message in such a way to cause directed cellular movement. Prokaryotic and eukaryotic chemotactic communication systems use different messages and transmitters to achieve the same outcome (i.e., cellular migration). The objective of this review is to highlight the similarities and differences of the chemotactic input for prokaryotic and eukaryotic systems

Figure 2

Messages and transmitters in prokaryotic and eukraryotic chemotactic systems. Chemotactic messages of prokaryotes and eukaryotes alike can be grouped by “type” (i.e., danger, communication, or nutrient signal) and each message is transmitted through an integral membrane protein shown here. Comparing the prokaryotic (A) messages shown (phenol, PDB ID: 5KBE; maltose, PDB ID: 1MPD; AI‐2, PDB ID: 2HJ9) to their eukaryotic (B) counterparts (cAMP, PDB ID:5KJY; folate, PDB ID 4QLE; chemokine IL‐8, PDB ID: 1IL8; LTB4, PDB ID 3ZUO; fMLP, PDB ID: 1Q7O; C5a, PDB ID: 5B4P), the increased molecular size and complexity of eukaryotic messages can be appreciated. All messages for Escherichia coli are transmitted through the common MCP Receptor architecture shown (from top to bottom; ligand binding domain, PDB ID:4Z9H; HAMP domain, PDB ID: 3ZX6; signaling domain, PDB ID: 3JA6; CheA and CheW, PDB ID: 3JA6) which is considerably larger that of the eukaryotic transmitter (i.e., GPCR). No structures are available for Dictyostelium discoideum GPCRs, G proteins, or arrestin domain‐containing proteins (ADC), so shown are mammalian examples (GPCR and G Protein, PDB ID: 3SN6; ADC, PDB ID: 4R7X). For mammalian neutrophils, shown is an example of a chemokine receptor (CCR5, PDB ID: 4MBS), the heterotrimeric G protein (PDB ID: 3SN6), and β‐arrestin 1 (PDB ID: 4JQI). Arrows shown indicate which proteins are thought to begin transmission through the noisy channel (i.e., begin the intracellular signaling cascades). The arrow below ADC is in light gray as it is unclear whether or not arrestin domain‐containing proteins play a role in Dictyostelium discoideum cAMP‐mediated chemotaxis

Figure 3

Comparison of communication circuitry among different organisms by message complexity. Chemotactic messages of different chemical complexity (i.e., small molecule, lipid, peptide, and protein) have different repertoire sizes (i.e., the number of ligands) and utilize unique circuitry to transmit their message. (A) Escherichia coli is used as an example to show the message, transmitter, and noisy channel architecture of each circuit. Messages (i.e., ligands) are shown as blue boxes. The transmitters (i.e., MCP receptors, Che proteins) are shown as gray boxes. Messages are connected to their corresponding transmitters via solid black lines, with uncertain or debated connections shown in gray. (B) Dictyostelium discoideum utilizes soley small molecule chemoattractant ligands, while (C) mammalian neutrophils utilize lipid, peptide, and protein messages. The G protein specificity of each message‐transmitter system is shown. Regardless of the specific message chemical complexity and receptor subtype, all systems seem to require Gαi/o for chemotactic signaling, though most also signal through other G protein subtypes (specifically, through the Gαq/11 family). The role of β‐arrestins in chemotactic signaling for many systems is still being elucidated (shown as gray arrows), but β‐arrestin 1 and β‐arrestin 2 have been shown to be required for chemokine‐mediated chemotactic signaling

Figure 4

Four principles to decode the chemotactic signal. Comparisons of chemoattractant‐receptor systems used by E. coli, D. discoideum, and neutrophils by message alphabet size (A), message complexity (B), transmitter capacity (C), and combinatorial complexity (D) demonstrate that chemoattractant receptor systems differentially encode complex chemotactic outcomes