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Cell Signaling
Cell signaling is the process by which extracellular stimuli are received, processed, and transported by the cell to regulate its own physiological responses. Cells in a multicellular organism communicate with one another to regulate tissue and organ development, to control their growth and division, and to coordinate their functions.
Phases of Cell Signaling
There are three stages in the process of cell signaling:
- Reception : It's the cell's detection of a signaling molecule ( ligand ) coming from outside of the cell. The signal is detected when the signaling molecule binds to the receptor located at the cell's surface or inside the cell. The signaling molecule is also known as primary messenger.
- Transduction : The receptor protein is changed when the signaling molecule binds to it which initiates the process of transduction. In transduction, a series of intermediary enzymes (relay molecules or secondary messengers) are activated downstream to transmit the signal to the site of action.
- Response : It's the stage of cell signaling where the signal finally triggers a specific cellular response.
Signaling Molecules (ligands): Signaling molecules are necessary for the coordination
of cellular responses by serving as ligands and binding to cell receptors.
*ligand : an ion, molecule, or functional group that binds to another chemical entity to form a larger complex.
Types of the Signaling Molecules
The types of molecules that serve as ligands are incredibly variable and range from small proteins to small ions like calcium.
1. Small Hydrophobic Ligands
Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are the steroid hormones, such as female sex hormone, estradiol; the male sex hormone, testosterone; and cholesterol. Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.
2. Water-Soluble Ligands
Water-soluble ligands are polar and, therefore, cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all. Instead, most water- soluble ligands bind to the extracellular domain of cell-surface receptors. These water soluble ligands are quite diverse and include small molecules, peptides, and proteins.
3. Other Ligands
Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane; one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue. NO has a very short half-life; therefore, it only functions over short distances. Nitroglycerin , a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart.
Types of Cell Receptors
Receptors are protein molecules in the target cell or on its surface that bind specific ligands, and are classified into two groups: internal receptors and cell-surface receptors. There are about 25 families of receptors in the human body. Each cell type in the body contains a distinctive set of cell surface and cytoplasmic receptor proteins that enable it to respond to a complementary set of signaling molecules in a specific, programmed way.
Types of Cell Surface Receptors
There are three general categories of cell-surface receptors:
1. Ion Channel-Linked Receptors
Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. When a ligand binds to the extracellular region of the channel, there is a conformational change in the protein’s structure that allows ions such as chloride ions and hydrogen ions to pass through.
2. Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme.
When a ligand binds to the extracellular domain, a signal is transferred through the membrane and activates the enzyme, which sets off a chain of events within the cell that eventually leads to a response. An example of this type of enzyme-linked receptor is the tyrosine kinase receptor.
3. G-Protein Linked Receptors
G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane.
3. Autocrine Signaling
Autocrine signals are signals that bind to receptors on the same cells that produced the signaling molecule. This means the signaling cell and the target cell can be the same or a similar cell. This type of signalling is important in immune response. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process.
4. Juxtacrine (Direct)Signaling:
In juxtacrine signaling, the signaling molecules are cell membrane-bound proteins which bind surface receptors of the target cell when the two cells make direct physical contact. This type of signaling is important during early embryonic development and tissue interactions. Another example of direct signaling is Gap junctions which are connections between the plasma membranes of neighboring cells. These water-filled channels allow small signaling molecules, called intracellular mediators, to diffuse between the two cells. Small molecules, such as calcium ions, are able to move between cells, but large molecules, like proteins and DNA, cannot fit through the channels. This allows a group of cells to coordinate their response to a signal that only one of them may have received.
Signaling Defects and Disease
A large number of diseases are caused by defects in signaling pathways. The nature of these defects and how they are induced varies enormously. Pathogenic organisms and viruses, many of which can interfere with signaling events, causing some of these defects. Most of the serious diseases in humans, such as hypertension, heart disease, diabetes and many forms of mental illness, seem to arise from subtle phenotypic modifications of signaling pathways. Such phenotypic remodeling alters the behavior of cells so that their normal functions are disrupted, leading to disease. Clearly, there is an urgent need to understand more about all of these disease states in order to design better therapies. A better understanding of cell signalling mechanisms offers many opportunities for discovering new ways of correcting many disease states.
