The images and text in this file are from Campbell, Reece, and Mitchell: Biology (5th edition, I think)

Cell Communication

Cells of the yeast Saccharomyces cerevisiae use chemical signaling to identify cells of opposite mating type and initiate the mating process.

1. Cells of mating type "a" release "a"-factor, which binds to receptors on nearby cells of mating type alpha. Meanwhile, alpha cells release alpha factor, which binds to specific receptors on a cells. (Both factors are peptides about 12 amino acids in length.)

2. Binding of the factors to receptors induces changes in the cells that lead to their fusion, or mating.

3. The resulting "a"/alpha. cell combines in its nucleus all the genes from the "a" and alpha cells.

Communication between mating yeast cells

(a) Animals have two main kinds of local chemical signaling. In paracrine signaling, a secreting cell acts on nearby target cells by discharging molecules of a local regulator into the extracellular fluid. In synaptic signaling, a nerve cell releases neurotransmitter molecules into a synapse, the narrow space between the transmitting cell and the target cell, here another nerve cell. (b) Hormones signal target cells at much greater distances. In animals, specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells, but, as with local regulators, only specific target cells recognize and respond to a given chemical signal. (Plants also use hormones for signaling from one part of the plant to another.)

Local and distant cell communication in animals

(a) Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

(b) Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Communication by direct contact between cells

From the perspective of the cell receiving the message, cell signaling can be divided into three stages: signal reception, signal transduction, and cellular response. When reception occurs at the plasma membrane, as shown here, the transduction stage is usually a pathway of several steps, with each molecule in the pathway bringing about a change in the next. The last molecule in the pathway triggers the cell's response.

Overview of cell signaling

(a) This type of receptor is a membrane protein that works in conjunction with a G protein and another protein, usually an enzyme. In the absence of the extracellular signal molecule specific for the receptor, all three proteins are in inactive form. The inactive G protein has a GDP molecule bound to it.

(b) When the signal molecule binds to the receptor, the receptor changes shape in such a way that it binds and activates the G protein. A molecule of GTP replaces the GDP on the G protein. The active G protein (moving freely along the membrane) binds to and activates the enzyme, which triggers the next step in the pathway leading to the cell's responses.

(c) The G protein then catalyzes the hydrolysis of its GTP and dissociates from the enzyme, becoming available for reuse. All three proteins remain attached to the plasma membrane.

The functioning of a G-protein-linked receptor

A large family of eukaryotic receptor proteins have this secondary structure: The single polypeptide, represented as a ribbon, has seven transmembrane alpha helices. Specific loops correspond to the sites where signal molecules and G-protein molecules bind. The alpha helices are depicted as cylinders for emphasis.

The structure of a G-protein-linked receptor

(a) In the absence of specific signal molecules, tyrosine-kinase receptors exist as single polypeptides in the plasma membrane. The extracellular portion of the protein, with the signal-molecule binding site, is connected by a single transmembrane a helix to the protein's cytoplasmic portion. This part of the protein is responsible for the receptor's tyrosine-kinase activity and also has a series of tyrosine amino acids.

(b) When signal molecules (such as a growth factor) attach to their binding sites, two polypeptides aggregate, forming a dimer. Using phosphate groups from ATP, the tyrosine-kinase region of each polypeptide phosphorylates the tyrosines on the other polypeptide. In other words, the dimer is both an enzyme and its own substrate. Now fully activated, the receptor protein can bind specific intracellular proteins, which attach to particular phosphorylated tyrosines and are themselves activated. Each can then initiate a signal-transduction pathway leading to a specific cellular response. Tyrosine-kinase receptors often activate several different signal-transduction pathways at once, helping regulate such complicated functions as cell reproduction (cell division). Inappropriate activation of these receptors can lead to uncontrolled cell growth--cancer.

The structure and function of a tyrosine-kinase receptor

This signal receptor is a transmembrane protein in the plasma membrane that opens to allow the flow of a specific kind of ion across the membrane when a specific signal molecule binds to the extracellular side of the protein.

A ligand-gated ion-channel receptor

This hypothetical signaling pathway begins when a signal molecule binds to a membrane receptor. The receptor then activates a relay molecule, which activates protein kinase 1. Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. In turn, active protein kinase 2 catalyzes the phosphorylation (and activation) of protein kinase 3. Finally, active protein kinase 3 phosphorylates a protein that brings about the cell's final response to the signal. The dashed arrows represent inactivation of the phosphorylated proteins, making them available for reuse; enzymes called phosphatases catalyze the removal of the phosphate groups. The active and inactive proteins are represented by different shapes to remind you that activation is usually associated with a change in molecular conformation.

A phosphorylation cascade

Cyclic AMP (cAMP) is made from ATP by adenylyl cyclase, an enzyme embedded in the plasma membrane. The enzyme is activated as a consequence of binding of a signal molecule (such as the hormone epinephrine) to a membrane receptor. Cyclic AMP functions as a second messenger that relays the signal from the membrane to the metabolic machinery of the cytoplasm. Cyclic AMP is inactivated by phosphodiesterase, an enzyme that converts it to inactive AMP.

Cyclic AMP

Cyclic AMP is a component of many G-protein-signaling pathways. The signal molecule--the "first messenger"--activates a G-protein-linked receptor, which activates a specific G protein. In turn, the G protein activates adenylyl cyclase, which catalyzes the conversion of ATP to cAMP. The cAMP then activates another protein, most often protein kinase A. The role of cAMP was discovered in research on a hormonal signal molecule, epinephrine.

cAMP as a second messenger

Calcium ions (Ca21) are actively transported out of the cytosol by a variety of protein pumps. Pumps in the plasma membrane move Ca21 into the extracellular fluid, and ones in the ER membrane move Ca21 into the lumen of the ER. Consequently, the Ca21 concentration in the cytosol is usually much lower (light blue) than in the extracellular fluid and ER (darker blue). Additional Ca21 pumps in the mitochondrial inner membrane operate when the calcium level in the cytosol rises significantly. These pumps are driven by the proton-motive force generated across the membrane by mitochondrial electron transport chains.

Calcium ion concentrations in an animal cell

Calcium ions (Ca21) and inositol trisphosphate (IP3) function as second messengers in many signal-transduction pathways. The process is initiated by the binding of a signal molecule to either a G-protein-linked receptor (left) or a tyrosine-kinase receptor (right). The circled numbers trace the former pathway. 1. A signal molecule binds to a receptor, leading to 2. activation of an enzyme called phospholipase C. 3. This enzyme cleaves a plasma-membrane phospholipid called PIP2 into DAG and IP3 (inset). Both can function as second messengers. 4. IP3, a small molecule, quickly diffuses through the cytosol and binds to a ligand-gated calcium channel in the ER membrane, causing it to open. 5. Calcium ions flow out of the ER (down their gradient), raising the Ca21 level in the cytosol. 6. The calcium ions activate the next protein in one or more signaling pathways, often acting via calmodulin, a ubiquitous Ca21-binding protein. DAG functions as a second messenger in still other pathways.

Calcium and inositol trisphosphate in signaling pathways

The stimulation of glycogen breakdown by epinephrine. (a) In this signaling system, the hormone epinephrine acts through a G-protein-linked receptor to activate a succession of relay molecules, including cAMP and two protein kinases. The final protein to be activated is the cytosolic enzyme glycogen phosphorylase, which releases glucose-1-phosphate units from glycogen. (b) As discussed in the next section of the text, this pathway amplifies the hormonal signal, because the receptor protein can activate many molecules of G protein, and each enzyme molecule in the pathway can act on many molecules of its substrate, the next molecule in the cascade. The number of activated molecules given for each step is only approximate.

Cytoplasmic response to a signal

The activation of a specific gene by a growth factor. This diagram is a simplified representation of a typical signaling pathway that leads to the regulation of gene activity in the cell nucleus. The initial signal molecule, a local regulator called a growth factor, triggers a phosphorylation cascade. The last kinase in the sequence enters the nucleus and there activates a gene-regulating protein, a transcription factor. This protein stimulates a specific gene to be transcribed into mRNA, which then directs the synthesis of a particular protein in the cytoplasm. Sometimes a transcription factor turns on several different genes.

Nuclear response to a signal

The particular proteins a cell possesses determine what signal molecules it responds to and the nature of the response. All four cells in these simplified diagrams respond to the signal molecule represented by the orange triangle, but in different ways, because each has a different set of proteins. Note, however, that the same kinds of molecules can participate in more than one pathway; for example, cells A, B, and C have identical receptors for the orange triangle. Cell B has a branched pathway, as is found especially often in pathways that use tyrosine-kinase receptors (which can activate multiple relay proteins) or second messengers (which can regulate numerous proteins). Cell C exhibits cross-talk between two pathways, enabling the cell to integrate information from two different signals. Cell D has a receptor for the orange triangle that differs from the ones in cells A, B, and C.

The specificity of cell signaling