Chemotaxis
|
|
Chemotaxis is the phenomenon in which bodily cells, bacteria, and other single-celled or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food (for example, glucose) by swimming towards the highest concentration of food molecules, or to flee from poisons (for example, phenol). In multicellular organisms, chemotaxis is critical in development as well as normal function. Additionally, it has been recognized that mechanisms that allow chemotaxis in animals can be subverted during cancer metastasis.
| Contents |
Bacterial chemotaxis
Bacteria, such as E. coli, have several flagella, usually six of them. These can rotate in two ways :
- Clockwise rotation means that every flagellum "paddles" into a different direction, causing the bacterium to tumble.
- Counter-clockwise rotation aligns the flagella into a single rotating bundle, causing the bacterium to swim in a straight line.
The overall movement of a bacterium is the result of altering tumble and swim phases. Chemotaxis steers the bacterium by regulating the tumbling frequency and duration. If the bacterium is in a favorable environment, the bacterium will tumble frequently so that net movement will be close to zero, while if the bacterium is in an unfavourable environment, it would tend to continue swimming in a straight line to leave the noxious environment. The helical nature of the individual flagellar filament is critical for this to occur. As such, the protein that makes up the flagellar filament, flagellin, is quite similar amongst all flagellated bacterium. Vertebrates seem to have taken advantage of this fact by possessing an immune receptor (TLR5)designed to recognize this conserved protein.
As in many instances in biology, there are bacterium that do not follow this rule. A class of bacterium called Helicobacter possess a single flagellum that is kept inside the cell wall. These bacteria move by spinning the whole cell, which is shaped like a corkscrew.
Signal transduction
A bacterium has three types of transmembrane receptors, for attractants, repellents and periplasmatic proteins. The signals from these receptors are transmitted across the plasma membrane into the cytosol, where che proteins are activated. The che proteins alter the tumbling frequency, and alter the receptors.
Flagellum regulation
The proteins CheW and CheA bind to the receptor. The activation of the receptor by an external stimulus causes autophosphorylation in CheA, which in turn phosphorylates CheB and CheY. CheY induced tumbling by interacting with the flagellum protein FliM.
Receptor regulation
CheB, which was activated by CheA, is a methylesterase, removes methyl residues from glutamate residues on the cytosolic side of the receptor. It works against CheR, a methyltransferase, which adds methyl residues to the glutamate residues. The more methyl residues are attached to the receptor, the more sensitive the receptor. As the signal from the receptor induces demethylation of the receptor in a feedback loop, the system is continuously adjusted to environmental chemical levels, remaining sensitive for small changes even under extreme chemical concentrations. This regulation allows the bacterium to 'remember' chemical concentrations from the recent past and compare them to those it is currently experiencing, thus 'know' whether it is travelling up or down a gradient.
Behaviour
The behaviour of the bacterium resulting from a basically simple mechanism appears quite complex. The bacterium follows an increasing attractant gradient, but starts changing direction once the concentration of the gradient decreases. This way, it finds the way to the area with the highest concentration of attractant (usually the source) quite well. Even under very high concentrations, it can still distinguish very small differences in concentration. Fleeing from a (poisonous) repellent works with the same efficiency. It remains remarkable that this purposeful random walk is a result of simply choosing between two methods of random movement, namely tumbling and straight swimming.
Eukaryotic chemotaxis
Some eukaryotic cells, such as immune cells also move to where they need to be. The mechanism by which eukaryotic cells chemotax is quite different than in bacteria.
Receptors
For the most part, eukaryotic cells sense the presence of chemotactic stimuli though the use of 7-transmembrane (or serpentine) heterotrimeric G-protein coupled receptors. This class of receptors is huge, representing a significant portion of the genome. Some members of this gene superfamily are used in eyesight (rhodopsins) as well as in olfaction (smelling).
Motility
Unlike motility in bacterial chemotaxis, the mechanism by which eukaryotic cells physcially move is unclear. There appears to be mechanisms by which an external chemotactic gradient is sensed and turned into an intracellular PIP2 gradient, but it is unclear how this leads to cellular motility.