An organism is a any system integrated by different parts having properties and functions related in a complex way that cooperate and interrelate with each other to attain the whole assembly main objectives.
Individual living things are called organisms and are capable of responding to external stimuli, fostering growth and reproducing while actively managing to maintain a dynamic equilibrium called Homeostasis.
The manner in which all the different components and levels (organs, tissues cells, etc.) can communicate with each other and work to produce appropiate responses to external (environmental) or internal demands in a highly sofisticated orchestration of physical, electrical and biochemical processes is called Cell Signaling.
Most cells in multicellular eukaryotes (just like ourselves) are both emitters and receivers of signals, although through specialization, respond only to signals for which they are individually equipped with apposite receptors to recognize, and trigger a physico-chemical process aimed at producing a required product or a change of some kind both intracellularly or outside the cell.
For instance, a motor neuron is a specialized, differentiated cell, located in the Central Nervous System (CNS). It projects part of its structure (axon) outside the CNS and into muscles, where an action potential ( the rapid rise and fall of an electrical voltage across the cell membrane) produces the desired movement in the muscle to which it connects.
By contrast, a peptic cell ( a cell that integrates the human stomach) is designed to synthetize and release both precursor and functional digestive enzymes upon receiving the appropiate signals, among which are the presence of Hydrochloric Acid in the stomach and the hormone Gastrin binding to the specific peptic cell receptor and unleashing the necessary intracellular process.
A way to classify the different intercellular signaling is:
- Endocrine, where endocrine cells secreting hormones into the bloodstream target distant cells. Testosterone (passes through plasma membrane and binds to a Cytosolic Receptor protein) and Insulin (binds to a Tyrosine Kinase Receptor at the plasma membrane) are examples of hormones travelling in the blood throughout the body.
- Paracrine, are signals produced intracellularly and released extracellularly to target near neighboring cells. Neuronal synapses function, either chemically or electrically or both, with this approach.
- Contact-dependent or Juxtacrine signals are transmitted along cell membranes into adjacent cells. Cell junctions connect adjacent cell cytoplasms where signaling substances dissolved in them travel freely and accomplish the required communication.
- Autocrine signals affect/target the cell itself. Inmune system cells responding to foreing antigens
The process of Cell Signaling involves three stages:
a chemical signal binds to a cellular protein, most frequently at the cell’s surface or inside the cell.
The cell targeted by a particular chemical signal has a receptor protein on or in the target cell that recognizes the signal molecule.Recognition effectively happens when the signal attaches to a specific site on the receptor molecule that is complementary in spatial shape to the signal molecule.
The signal molecule behaves as a ligand, a molecule that binds with non-absolute specificity to a larger receptor molecule (most often a protein) forming a larger complex transitory assembly.
Ligand binding causes the receptor protein to undergo a change in shape wchich activates the receptor so that it can interact with other molecules.
For other receptors, this causes aggregation of receptor molecules, leading to further molecular events inside the cell.
Most signal receptors are plasma membrane proteins, whose ligands are large water-soluble molecules that are too large to cross the plasma membrane. These are comprised of :
- More than 1000 sub types are called G Protein-Coupled receptors
binding leads to a change in the receptor that unleashes a series of changes in a series of different molecules along a signal-transduction pathway. The molecules in the pathway are called relay molecules.
The transduction stage of signaling is usually a multistep pathway which often amplify significantly the original signal.
Analogous to a chain reaction, when a molecule in a pathway transmits a signal to multiple molecules in the next level of the transduction path, it results in large numbers of activated molecules at the end of the pathway.
As a consequence of this design, a small number of signal molecules often produce a large cellular response while providing more opportunities for coordination and regulation along the transduction path than simpler/shorter systems might allow .
Pathways relay signals from receptors to ultimately produce cellular responses.
The relay molecules that transmit a signal from receptor to response are also mostly proteins. This protein interaction is the cornertone of signal transduction.
As the original signal molecule frequently does not pass through the plasma membrane, along the pathway it transfers information (signal) and at each step, the signal is transduced into a different form achieved by a conformational change in the current step transducing protein.
The conformational change is most often accomplished by a molecular addition called phosphorylation . The phosphorylation of proteins by a specific enzyme (a protein kinase) is a widespread cellular mechanism for regulating protein activity.
Most protein kinases act on other substrate protein at either serine and threonine amino acids of the substrate protein.
Many of the relay molecules in a signal-transduction pathway are protein kinases that act on other protein kinases to create a “phosphorylation cascade.”
Each protein phosphorylation leads to a conformational change because of the interaction between the newly added phosphate group and charged or polar amino acids on the protein. Phosphorylation of a protein typically converts it from an inactive form to an active form.
A single cell may have hundreds of different protein kinases, each specific for a different substrate protein.
The responsibility for turning off a signal-transduction pathway belongs to protein phosphatases. These enzymes rapidly remove phosphate groups from proteins, a process called dephosphorylation .
Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to the same signal. At any time, the net activity of a protein regulated by phosphorylation depends on the balance of active kinase and phosphatase molecules versus the inactive ones.
When the extracellular signal molecule is absent from the binding site, active phosphatase molecules predominate, and the signaling pathway and cellular response are off.
As it turns out, the phosphorylation /dephosphorylation system acts as a molecular switch in the cell, turning activities on and off as required.
Other than protein molecules and ions are key components of signaling pathways too.
Many signaling pathways involve small, water-soluble, nonprotein molecules or ions called second messengers. These molecules rapidly diffuse throughout the cell.
Second messengers participate in pathways initiated by both G-protein-linked receptors and tyrosine-kinase receptors.
Two of the most widely used second messengers are cyclic AMP (adenosine monophosphate) and the ion of calcium Ca2+.
Protein Kinase A, PKA , for instance, is a cAMP dependent kinase, meaning that its phosphorilation activity on other enzymes is directly dependent on cAMP concentrations present. PKA is responsible, among other multiple functions, for the breakdown of glycogen into glucose in liver and muscle tissue. Also, its levels regulate smooth muscle contractility level and some proteases activity (collagenase for one).
On the other hand, cells use Ca2+ as a second messenger in both G-protein pathways and tyrosine-kinase pathways.
The Ca2+ concentration in the cytosol is typically much lower than that outside the cell, often by a factor of 10,000 or more. Various protein pumps transport Ca2+ outside the cell or into the endoplasmic reticulum (ER) or other organelles. As a result, the concentration of Ca2+ in the ER is usually much higher than the concentration in the cytosol.
Because cytosolic Ca2+ is so low, small changes in the absolute numbers of ions causes a relatively large percentage change in Ca2+ concentration.
Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.
As an example, intracellular calcium release from the sarcoplasmic reticulum (SR) is required for cardiac muscle contraction. In fact, with each heart beat, the Ca2+ concentration in the cytosol of cardiac myocytes is increased tenfold from its baseline. Immediately after the beat, this very same concentration of Ca2+ must be lowered to the baseline level so that it allows the heart chamber to relax and refill with blood in preparation for the next beat.
Finally, the cell responds to the signal by activating cellular processes that lead to, among many others:
- New protein synthesis
- Regulation of protein activity
- Glycogen breakdown
- Programmed cell death (apoptosis)
- Increase heart beat
- Regulation of gastric and intestinal motility
As important as activating mechanisms are inactivation mechanisms. For a cell to be ready and capable of responding to an incoming signal, each molecular change in its signaling pathways must last only a short time and must be a reversible one, allowing the receptors to return to their inactive state when the signal molecule is released or not present any longer.