Within every organism is a huge array of cells that perform different functions. In order to synchronize these functions and respond to stimuli, cells have means of communicating through various chemical signals over many different distances. Cell signaling is beneficial because it elicits a rapid response: rather than waiting for a signal to diffuse into the cell, the cell can respond to an extracellular stimulus quickly. Additionally, cell signaling amplifies a small stimulus which allows for a large response from a small signal. Signals can cause many different responses in cells from changes in gene expression (resulting in transcription of different proteins) or apoptosis.
The basis of cell signaling involves the presence of molecules to trigger a response. This means that cells, usually in the cell membrane, are lined with various receptors that respond to the presence of certain molecules. There are three main types of receptors: G-Protein linked, ligand gated ion channels, and protein (tyrosine) - kinase receptors.
In G protein receptors, a response is triggered when a ligand bonds to the receptor on the outside of the cell. The signal must be the specific molecule that the receptor responds to. The binding of the signal causes a GTP molecule (similar to ATP) to phosphorylate an intracellular protein by attaching its phosphate group and becoming GDP. This first phosphorylation triggers a phosphorylation cascade which activates an increasing number of proteins which amplifies the original signal.
Additionally, in a foundational experiment, John Sutherland discovered that a cell signaling pathway only functions properly when a cell is intact. This pointed to the discovery of secondary messengers like cAMP or ions like Ca2+. These secondary messengers are often released when the initial signal is received which helps propagate the signal even farther.
Ligand gated ions channels are made up of a gate-like passage in the cell membrane which is typically closed to prevent ions from entering the cell. However, when a signal molecule is present, the gate opens up and ions can enter the cell through the protein channel.
Protein-kinase or tyrosine-kinase receptors are two part proteins (dimers). When a signal is present, the two proteins come together and phosphorylate each other which causes a reaction within the cell resulting in signal propagation.
The shortest distance of cell to cell communication occurs when cell touch. One example of cell to cell contact is plasmodesmata in plants. Plasmodesmata are small holes in the cell walls of plant cell that open up into other cells. Plant cells can pass signal molecules from one cell to another without having to cross into any extracellular space. Similarly animal cells have analogous gap junctions between adjacent cell membranes. Another example is T cells and B cells in the immune response. T cells and B cells respond to specific proteins on the outside of viruses or bacteria to create the immune response which is only possible when these cells come into contact with the antigen itself.
Local or paracrine signaling occurs between cells that are close to one another. One example of local signaling is neural synapses. Nerve cells use the sodium potassium pump to create a resting voltage differential of -70mv between the inside and the outside of the cell. When a signal crosses the threshold, a positive feedback loop opens sodium ion channels which cause sodium ions that had been pumped out to flow into the cell through facilitated diffusion. This causes a huge spike in the voltage potential of the cell which triggers this action potential to continue spreading through the nerve cell.
Local signaling occurs when the action potential reaches the axon terminal.Two nerve cells do not touch at the signaling end; rather, there is a small gap between them called the synaptic cleft. The axon terminal released short-distance signals called neurotransmitters into the synaptic cleft. These signals are picked up by receptors on the receiving neuron which then continue to spread the action potential.
Long distance signals occur when a signal molecule spreads throughout an entire organism. Hormones are an example of long distance signaling. For example, growth hormone is released from the pituitary gland but spreads throughout the entire body, resulting in a response from all parts of the organism.
The cell cycle is the process through which cells multiply. Cells divide through a process called mitosis which yields two identical daughter cells to the parent cell. Mitosis allows multicellular organisms to grow or replace old cells and allows single celled organisms to reproduce. Mitosis makes up one part of the cell cycle
The cell cycle begins in G1 when a cell grows, copies organelles, and prepares itself to divide. Next, in the S phase, the cell’s DNA is copied. This process is explained further on the gene expression page. Next, during G2, the cell makes final preparations to divide by making more proteins and organelles while reorganizing its contents before mitosis. G1, S, and G2 are called interphase when combined together.
Mitosis itself begins with prophase. During prophase, chromosomes begin to condense and the mitotic spindle begins to form. The nucleolus, a part of the nucleus where ribosomes are made, also disappears which shows that the cell is ready to divide. Later in prophase, the chromosomes are fully condensed and the nuclear envelope, the membrane surrounding the nucleus, breaks down. Next, during metaphase, each condensed chromosomes attaches to a mitotic spindle and is lined up in the middle of the cell. The paired chromosomes (sister chromatids) are held together at the centromere and the spindle attaches to each chromosome at the kinetochore. During anaphase, the mitotic spindles holding each sister chromatid retract which splits the paired chromosomes and pulls half to one side and half to the other side, thus evenly splitting the genetic material of the parent cell into two distinct regions that will become the daughter cells. During telophase, the cell’s normal structures reform. The mitotic spindle fibers disappear, and two nuclear membranes begin to form. Finally, during cytokinesis, the cell splits. In an animal cell, an actin ring pinches the cell membrane which creates a cleavage furrow. As the actin ring tightens, the cell membrane splits. In a plant cell, a cell plate grows between the two nuclei to create a new cell wall to divide the cells. After cytokinesis, the cell returns to G1.
Sometimes, when a cell is in a functional stage or is no longer dividing, it can enter G0. A cell in G0 still functions normally, but it no longer grows and divides as it stops progressing through the cell cycle. Neuron cells are a common example of cells in G0 because once they form nerve fibers, neurons no longer divide.
The G1 checkpoint before the cell moves into the S phase ensures that the cell is prepared to replicate its DNA and divide. This is also where a cell can enter G0, either to perform its function or to remedy an issue that prevents it from dividing. This checkpoint is based mostly on environmental factors. The RAS protein signaling pathway (explained below) results in the expression of DNA that codes for Cyclin Dependent Kinase proteins. These proteins form mitosis promoting factor which satisfies this checkpoint and allows the cell to continue through the cell cycle.
The G2 checkpoint ensures that the cell should divide based on its internal factors. DNA is checked to make sure it replicated properly and is undamaged. Like the G1 checkpoint enough CDKs signal the cell to progress into mitosis.
The metaphase checkpoint ensures that the chromosomes lined up properly. Any issue in lining up would cause an uneven split of genetic material into the daughter cells.
RAS is a protein in a G Protein linked receptor pathway. When a signal activates the RAS protein, a phosphorylation cascade occurs which results in gene expression of proteins that stimulate cell growth and development. p53 is a transcription factor, meaning that it is a protein created at the end of a cell signaling pathway. p53 tells a cell to stop dividing. In defective cells which often lead to cancerous tumors, both RAS and the p53 pathway are mutated. RAS becomes hyperactive and gives constant signals for the cell to divide, while p53 becomes inactive and no longer tells the cell to stop. By always being told to divide and never being told to stop, the cell will rapidly divide, leading to a tumor.
Normal cells have density and anchorage dependence. Density dependence means that when there is a certain pressure on a cell from the cells around it, the cell will stop dividing. Similarly, anchorage dependence requires that a cell be connected to at least one other surface in order for it to divide. Cancer cells do not have either of these factors. Without density dependence, cancer cells continue to divide which creates a tumor. Additionally, the lack of anchorage dependence allows cancer cells to easily metastasize.
Organisms respond to their environments and preserve internal conditions through feedback loops. A negative feedback loop maintains homeostasis by forcing a system to return to its original condition if this condition is changed. For example, the control of blood sugar is a negative feedback loop. If blood sugar is too high, insulin is released, and if blood sugar is too low, glucagon is released in order to return blood sugar levels to their normal range. Other negative feedback loops occur in temperature regulation and osmoregulation.
Positive feedback loops occur when a reaction causes more of that reaction to occur. One example is fruit ripening. One fruit ripens which releases ethylene gas, and the ethylene serves as a signal to other fruits to ripen, which in turn releases more ethylene gas. Other examples of positive feedback loops are contractions in childbirth and blood clotting.