Since it would do an organism little good to have so many tiny entities toiling in isolation from one another, cells must have a means of communicating with each other – that is, both sending and receiving signals. Lacking radio, television and the Internet, cells engage in signal transduction, using old-fashioned chemicals.
Just as scrawling letters or words on a page is not helpful unless these characters and entities form words, sentences and a coherent, unambiguous message, chemical signals are of no use unless they contain specific instructions.
For this reason, cells are equipped with all manner of clever mechanisms for the generation and transduction (that is, transmission through a physical medium) of biochemical messages. The ultimate goal of cell signaling is to influence the creation or modification of gene products, or proteins made on the ribosomes of cells in accordance with information coded in DNA via RNA.
Reasons for Signal Transduction
If you were one of dozens of drivers for a taxicab company, you'd need the skills to drive a car and navigate the streets of your city or town knowledgeably and skillfully in order to meet your passengers on time in the right spot and get them to their destinations when they want to be there. This, however, would not be enough on its own if the company hoped to operate at maximum efficiency.
Drivers in different cabs would need to communicate with each other and with a central dispatcher to determine what passengers should be picked up by whom, when certain cars were full or otherwise unavailable for a spell, stuck in traffic and so on.
Absent the ability to communicate with anyone other than potential passengers via telephone or online app, the business would be chaotic.
In the same spirit, biological cells cannot operate in complete independence of the cells around them. Often, local clusters of cells or entire tissues need to coordinate an activity, such as a muscular contraction or healing after a wound. Thus cells have to communicate with each other to keep their activities aligned with the needs of the organism as whole. Absent this ability, cells cannot properly manage growth, movement and other functions.
Deficits in this area can lead to grave consequences, including diseases such as cancer, which is essentially unchecked cell replication in a given tissue owing to an inability of cells to modulate their own growth. Cell signaling and transduction of signals is therefore vital to the health of the organism as a whole as well as of the affected cells.
What Happens During Signal Transduction
Cell signaling can be divided into three basic phases:
- Reception: Specialized structures on the cell surface detect the presence of a signaling molecule, or ligand.
- Transduction: The binding of the ligand to the receptor initiates a signal or cascading series of signals on the interior of the cell.
- Response: The message signaled by the ligand and the proteins and other elements it influences is interpreted and put into process, such as via gene expression or regulation.
Like organisms themselves, a cell signal transduction pathway can be exquisitely simple or comparatively complex, with some scenarios involving just one input or signal, or others entailing a whole series of sequential, coordinated steps.
A bacterium, for example, lacks the capacity to deliberate over the nature of safety threats in its environment, but it can sense the presence of glucose, the substance all prokaryotic cells use for food.
More complex organisms send signals using growth factors, hormones, neurotransmitters and components of the matrix between cells. These substances can act on nearby cells or at a distance by traveling though the blood and other channels. Neurotransmitters such as dopamine and serotonin traverse the the small spaces between adjacent nerve cells (neurons) or between neurons and muscle cells or target glands.
Hormones often act at especially long distances, with hormone molecules secreted in the brain exerting effects on the gonads, adrenal glands and other "faraway" tissues.
Cell Receptors: Gateways to the Signal Transduction Pathway
Just as enzymes, the catalysts of cellular biochemical reaction, are specific for certain substrate molecules, the receptors on the surfaces of cells are specific for a particular signal molecule. The level of specificity can vary, and some molecules can weakly activate receptors that other molecules can activate strongly.
For example, opioid painkiller drugs activate certain receptors in the body that natural substances called endorphins also trigger, but these drugs usually have a far stronger effect owing to their pharmacological tailoring.
Receptors are proteins, and reception takes place on surface. Think of receptors as cellular doorbells.it like a doorbell. Doorbells are outside your house and activating it is what causing people in your house to answer the door. But in order for it the doorbell to work, someone must use their finger to press the bell.
The ligand is analogous to the finger. Once it binds to the receptor, which is like the doorbell, it will start the process of the internal workings/signal transduction just as the doorbell triggers those inside the house to move and answer the door.
While the ligand binding (and the finger pressing the doorbell) is essential to the process, it is only the start. A ligand binding to a cell receptor is only the start of a process whose signal must be modified in strength, direction and ultimate effect in order to be helpful to the cell and the organism in which it resides.
Reception: Detecting a Signal
Cell membrane receptors include three major types:
- G-protein-coupled receptors
- Enzyme-linked receptors
- Ion channel receptors
In all cases, the activation of the receptor initiates a chemical cascade that dispatches a signal from the exterior of the cell, or on a membrane within the cell, to the nucleus, which is the de facto "brain" of the cell and the locus of its genetic material (DNA, or deoxyribonucleic acid).
The signals travel to the nucleus because their objective is to in some way influence gene expression – the translation of the codes contained in genes to the protein product that the genes code for.
Before the signal gets anywhere near the nucleus, it is interpreted and modified near the site of its origin, at the receptor. This modification may involve amplification through second messengers, or it may mean a slight diminishing of the signal strength if the situation demands it.
G proteins are polypedtides with unique amino acid sequences. In the cell signal transduction pathway in which they participate, they usually link the receptor itself to an enzyme that carries out the instructions pertinent to the receptor.
These make use of a second messenger, in this case cyclic adenosine monophosphate (cyclic AMP, or cAMP) to amplify and direct the signal. Other common second messengers include nitric oxide (NO) and calcium ion (Ca2+).
For example, the receptor for the molecule epinephrine, which you recognize more readily as the stimulant-type molecule adrenalin, causes physical changes to a G-protein adjacent to the ligand-receptor complex in the cell membrane when epinephrine activates the receptor.
This, in turn, causes a G-protein to trigger the enzyme adenylyl cyclase, which leads to cAMP production. cAMP then "orders" an increase in an enzyme that breaks down glycogen, the cell's storage form of carbohydrate, to glucose.
Second messengers often send distinct but consistent signals to different genes in the cell DNA. When cAMP calls for the degradation of glycogen, it simultaneously signals for a rollback in the production of glycogen via a different enzyme, thus reducing the potential for futile cycles (the concurrent unfolding of opposed processes, such as running water into one end of a pool while trying to drain the other end).
Receptor Tyrosine Kinases (RTKs)
Kinases are enzymes that take phosphorylate molecules. They accomplish this by moving a phosphate group from ATP (adenosine triphosphate, a molecule equivalent to AMP with two phosphates appended to the one AMP already has) to a different molecule. Phosphorylases are similar, but these enzymes pick up free phosphates rather than grab them from ATP.
In cell-signal physiology, RTKs, unlike G-proteins, are receptors that also possess enzymatic properties. In short, the receptor end of the molecule faces the outside of the membrane, while the tail end, made from the amino acid tyrosine, has the ability to phosphorylate molecules inside the cell.
This leads to a cascade of reactions that direct the DNA in the cell nucleus to up-regulate (increase) or down-regulate (decrease) the production of a protein product or products. Perhaps the best-studied such chain of reactions is the mitogen-activated protein (MAP) kinase cascade.
Mutations in PTKs are believed to be responsible for the genesis of certain forms of cancer. Also, it should be noted that phosphorylation can inactivate as well as activate target molecules, depending on the specific context.
Ligand-Activated Ion Channels
These channels consist of an "aqueous pore" in the cell membrane and are made from proteins embedded in the membrane. The receptor for the common neurotransmitter acetylcholine is an example of such a receptor.
Rather than generating a cascading signal per se within the cell, acetylcholine binding to its receptor causes the pore in the complex to widen, allowing ions (charged particles) to flow into the cell and exert their effects downstream on protein synthesis.
Response: Integrating a Chemical Signal
It is vital to recognize that the actions that occur as part of cell-receptor signal transduction are not typically "on/off" phenomena. That is, the phosphorylation or dephosphorylation of a molecule does not determine the range of possible responses, either at the molecule itself or in terms of its downstream signal.
Some molecules, for example, can be phosphorylated at more than one location. This provides tighter modulation of the action of the molecule, in the same general manner that a vacuum cleaner or blender with multiple settings can allow for more targeted cleaning or smoothie-making than a binary "on/off" switch.
In addition, every cell has multiple receptors of each type, the response of each of which must be integrated at or before the nucleus to determine the overall magnitude of the response. Generally, receptor activation is proportional to the response, meaning that the more ligand that binds to a receptor, the more marked the alterations within the cell are likely to be.
This is why when you take a high dose of a medication, it usually exerts a stronger effect than a smaller dose. More receptors are activated, more cAMP or phosphorylated intracellular proteins result, and more of whatever is required in the nucleus takes place (and often happens faster as well as to a greater extent).
A Note on Gene Expression
Proteins are made after DNA makes a coded copy of its already encoded information in the form of messenger RNA, which moves outside the nucleus to ribosomes, where proteins are actually made from amino acids in accordance with the instructions supplied by mRNA.
The process of making mRNA from a DNA template is called transcription. Proteins called transcription factors can be up-regulated or down-regulated as a result of the input of various independent or simultaneous transduction signals. A different amount of the protein that the gene sequence (length of DNA) codes for is synthesized as a result.
- NCBI Bookshelf: Molecular Cell Biology (4th Edition): Interaction and Regulation of Signaling Pathways
- Scitable by Nature Education: Cell Signaling
- NCBI Bookshelf: The Cell: A Molecular Approach (2nd Edition): Pathways of Intracellular Signal Transduction
- Scitable by Nature Education: Gene Expression and Regulation
- Scitable by Nature Education: RTK