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Cell Communication. Chapter 11. 11.1 – External signals are converted to responses within the cell. Evolution of cell signaling. Signal transduction pathway: process by which a signal on a cell’s surface is converted to a certain cellular response in a series of steps.
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Cell Communication Chapter 11
11.1 – External signals are converted to responses within the cell
Evolution of cell signaling • Signal transduction pathway: process by which a signal on a cell’s surface is converted to a certain cellular response in a series of steps. • Many of these pathways have been researched extensively in both yeast and animal cells. • These signal transduction pathways in both cells seem to have remarkably similar molecular characteristics.
Cell-Cell Recognition • Both animals and plants have cell junctions that let molecules to pass between adjacent cells without crossing plasma membranes. • Two cells in an animal may communicate by interaction between molecules that protrude from their surfaces – cell-cell recognition. • Local regulators are messenger molecules that travel short distances to influence cells in the area. • Growth factors are one class of local regulators in animals; they stimulate nearby cells to grow and divide.
Local and Long-distance Signaling • Two types of local signaling: paracrine signaling and synaptic signaling. • Paracrine signaling occurs when a cell secretes molecules of a local regulator into the extracellular fluid of a target cell. • Synaptic signaling occurs when a neuron secretes molecules of a neurotransmitter into a synapse, which stimulates the target cell. • Hormonal signaling is a type of long-distance signaling that occurs when endocrine cells secrete hormones into body fluids.
The Three stages of cell signaling • Earl W. Sutherland’s early work of signal transduction pathways suggested that the process that occurs at the receiving end of a cellular conversation can be divided into three stages: • Reception: the detection of a chemical signal when the signaling molecule binds to a receptor protein that is often located at the surface of the cell’s surface or inside the cell. • Transduction: converts signal to a form that can produce a certain response; may occur in a single step but usually occurs in a series of changes with different molecules (relay molecules). • Response: the triggering of a cellular response by the transduced signal.
11.2 – Reception: A signaling molecule binds to a receptor protein, causing it to change shape
Receptors in the Plasma Membrane • A signaling molecule behaves as a ligand. • Three major types of membrane receptors: G protein-coupled receptors, receptor tyrosine kinases, and ion channel receptors. • G protein-coupled receptors are plasma membrane receptors that work with the help of G proteins, which are proteins that bind the energy-rich molecule GTP. • Receptor tyrosine kinases belong to a major class of plasma membrane receptors characterized by having enzymatic activity. • A kinase is an enzyme that catalyzes the transfer of phosphate groups. • A ligand-gated ion channel is a type of membrane receptor containing a region that can act as a “gate” when the receptor changes shape. • When a signaling molecule binds as a ligand to the receptor protein, the gate opens or closes, allowing or blocking the flow of specific ions, such as Na+ or Ca2+, through a channel in the receptor. • Intracellular receptor proteins are found in either the cytoplasm or the nucleus of target cells.
11.3 – Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Signal Transduction Pathways • Like falling dominoes, the signal-activated receptor activates another molecule, which activates yet another molecule, and so on, until the protein that produces the final cellular response is activated. • Protein interaction is a unifying theme of all regulation at the cellular level. • At each step in a pathway, the signal is transduced into a different form, commonly a shape change in a protein.
Protein phosphorylation and dephosphorylation • The phosphorylation and dephosphorylation of proteins is a widespread cellular mechanism for regulating protein activity. • A protein kinase is an enzyme that transfers phosphate groups from ATP to a protein. • In a phosphorylation cascade, a series of different molecules in a pathway are phosphorylated in turn, each molecule adding a phosphate group to the next one in line. • Protein phosphatases are enzymes that can rapidly remove phosphate groups from proteins, a process called dephosphorylation. • By dephosphorylating and inactivating protein kinases, phosphatases provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present.
Small molecules and ions as second messengers • Many signaling pathways involve small, nonprotein, water-soluble molecules or ions called second messengers. • They can easily be spread throughout the cell by diffusion. • The two most widely used second messengers are cyclic AMP and calcium ions. • In Sutherland’s studies, he found that the binding of epinephrine to the plasma membrane of a liver cell elevates the cytosolic concentration of cyclic adenosine monophosphate, or cAMP. • An enzyme in the plasma membrane, adenylyl cyclase, converts ATP to cAMP in response to an extracellular signal. • Many G proteins activate adenylyl cyclase that makes cAMP from ATP. • Cells use calcium ions as second messengers in both G-protein and tyrosine kinase pathways. • The tyrosine kinase pathways can also incorporate two other second messengers, diacylglycerol (DAG) and inositol triphosphate (IP3). The latter can trigger a subsequent increase in calcium ion levels.
11.4 – Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
Nuclear and Cytoplasmic responses • Some pathways regulate genes by activating transcription factors, proteins that turn specific genes turn on or off. • In the cytoplasm, signaling pathways regulate, for example, enzyme activity and cytoskeleton rearrangement, which can lead to cell shape changes.
Fine-Tuning of the response • Each catalytic protein in a signaling pathway amplifies the signal by activating multiple copies of the next component of the pathway. • For long pathways, the total amplification may be a millionfold or more. • The particular combination of proteins in a cell gives the cell great specificity in both the signals it detects and responses it carries out. • Scaffolding proteins can increase signal transduction efficiency. • They are large relay proteins to which several other relay proteins are simultaneously attached. • Pathway branching and cross-talk further help the cell coordinate incoming signals. • Signal response is terminated quickly by the reversal of ligand blinding.
11.5 – Apoptosis (programmed cell death) integrates multiple cell-signaling pathways
Apoptosis (programmed cell death) • Apoptosis is a type of programmed cell death in which cell components are disposed of in an orderly fashion without damage to neighboring cells. • Apoptosis occurs at defined times during embryonic development of C. elegans(soil worm). • A protein (ced-9) in the mitochondrial membrane acts as a brake; when released by a death signal, it allows activation of caspases that carry out apoptosis. • Several apoptotic pathways exist in the cells of humans and other mammals, and these pathways may be triggered in different ways.
Short Answer Questions • Describe the different types of local and long-distance signaling. Define, explain, and give an example of local regulators. • A signal transduction pathway has three stages. Explain each step. • Explain the role of these enzymes in transduction: • Protein kinase • Protein phosphatase
Answers • Describe the different types of local and long-distance signaling. Define, explain, and give an example of local regulators. • Hormonal • Long distance • Release of hormones (chemical that works over long periods of time) throughout the blood stream into specific cells • Synaptic • Local • Transmission of a message from a nerve cell to other cells(nerves or muscles) via a chemical (neurotransmitters) • Paracrine • Local • How all other cells communicate with each other. Can be chemical or via junctions
Answers • A signal transduction pathway has three stages. Explain each step. • Step 1 – Reception • Message is received when signal molecules bind to receptor proteins on or in the cell • Step 2 – Transduction • Message goes through a phosphorylation cascade which converts the signal received into a response(or trigger for) • Step 3 – Response • The carrying out of the message sent
answers • Explain the role of these enzymes in transduction: • Protein kinase • Attaches the phosphates onto the ADP • Protein phosphatase • Removes phosphates from ATP