![]() However, the term ‘second messenger’ seems somewhat outdated, since a signalling pathway can easily involve a sequence of eight or more different messengers, and the ‘second messenger’ in question could well actually be acting as, say, the fifth messenger. Second messengers were the first intracellular signalling molecules to be identified they were so named because hormones or other extracellular signalling molecules were considered the ‘first messengers’. Ca 2+ achieves this by binding to an inhibitory protein complex of tropomyosin and troponin, which under resting conditions prevents actin and myosin filaments from interacting. (e) The increase of Ca 2+concentration throughout the sarcoplasm enables the rapid and synchronous contraction of the muscle filaments. (d) This more general depolarization triggers the very rapid release of Ca 2+ions into the sarcoplasm (muscle cytoplasm) through voltage-gated Ca 2+ channels from stores in the sarcoplasmic reticulum the Ca 2+ions spread through the muscle cell. ![]() (c) Depolarization is propagated in the muscle cell (yellow arrows) by voltage-gated Na + channels, which allow further Na + ion entry. (b) These receptors are ion channels, and so promote local depolarization (an increase in membrane potential caused by the entry of sodium ions). (a) Acetylcholine (ACh, shown in pink) is released from the neuron terminal, and binds to ACh-gated Na + channels on the surface of the muscle cell. Other water-soluble second messengers such as cAMP and cGMP act similarly to Ca 2+, by diffusing through the cytosol, whereas second messengers such as diacylglycerol (DAG) are lipid-soluble, and diffuse along the inside of the plasma membrane, in which are anchored various other key signalling proteins.įigure 7 Calcium ions help to synchronize the rapid contraction of skeletal muscle cells. In general, if a rapid, generalized response is necessary, a second messenger is likely be prominent in the signalling pathway. For example, Ca 2+ ions mediate and coordinate contraction of skeletal muscle cells ( Figure 7). Ca 2+ ions can therefore broadcast the signal quickly to several distant parts of the cell. The calcium ion, Ca 2+, is a classic example of a second messenger, being released in large quantities in response to a signal (so amplifying the signal) and diffusing rapidly through the cytosol. Second messengers are small readily diffusible intracellular mediators, whose concentration inside the cell changes rapidly on receptor activation in this manner, they regulate the activity of other target signalling molecules. A typical signalling pathway will involve many of these components. This figure illustrates all the types of interaction involving signalling proteins and second messengers, leading to cellular responses, in this case expression of a target gene and/or changes in the cytoskeleton (via the anchoring protein). Broadly speaking, intracellular signalling molecules can be divided into two groups on the basis of molecular characteristics, second messengers and signalling proteins.įigure 6 Signal transduction pathways are not simple chains, but highly complex, branching pathways, involving many different types of signalling proteins (including scaffold proteins, relay proteins, bifurcation proteins, adaptor proteins, amplifier and transducer proteins, integrator proteins, modulator proteins, messenger proteins and target proteins) and small intracellular mediators known as second messengers. Intracellular signalling molecules have particular properties that allow control of the speed, duration and target of the signal, and may be categorized according to these properties. The branched molecular network of activation (and deactivation) of signalling molecules linking receptor activation to the intracellular targets is referred to as a signal transduction pathway (or cascade). In reality, of course, it is rarely a simple chain, but a branching network, allowing for integration, diversification and modulation of responses ( Figure 6). We have already described a simple signalling model (Figure 2), where a chain of intracellular mediators successively activates the next in the chain until the target is reached. So, signal transduction needs to take place over both space and time. The transmission of a signal must occur in a time-frame appropriate for the cellular response. Signalling information has to be transmitted from the receptor in the plasma membrane across the cytoplasm to the nucleus (if gene transcription is the response), the cytoskeleton (if cell movement, or another change to cell morphology, is the response), or various other subcellular compartments.
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