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AP Biology 12: Cell signaling/ cell to cell communication Name: ___________ References: 1. Campbell Biology chapter 11 2. College Board Cell to cell special focus. Big Idea 2: Biological systems utilize free energy and molecular building blocks to grow, to reproduce and to maintain dynamic homeostasis. Essential knowledge: 2.e.2 Timing and coordination of physiological events are regulated by multiple mechanisms. Illustrative examples covered: • Circadian rhythms, or the physiological cycle of about 24 hours that is present in all eukaryotes and persists even in the absence of external cues • Diurnal/nocturnal and sleep/awake cycles • Jet lag in humans • Seasonal responses, such as hibernation, estivation, and migration • Release and reaction to pheromones • Visual displays in the reproductive cycle • Fruiting body formation in fungi, slime molds and certain types of bacteria • Quorum sensing in bacteria Reference: Campbell 11.1 Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes. Essential knowledge: 3.B.2 A variety of intercellular and intracellular signal transmissions mediate gene expression. Illustrative examples covered: • Cytokines regulate gene expression to allow for cell replication and division • Mating pheromones in yeast trigger mating gene expression • Levels of cAMP regulate metabolic gene expression in bacteria • Expression of the SRY gene triggers the male sexual development pathway in animals • Ethylene levels cause changes in the production of different enzymes, allowing fruits to ripen • Seed germination and gibberellin • Mating pheromones in yeast trigger mating genes expression and sexual reproduction • Morphogens stimulate cell differentiation and development • Changes in p53 activity can result in cancer • HOX genes and their role in development Reference: Campbell 11.1 and 11.4 AP Biology Cell to cell communication Page 1 Essential knowledge: 3.D.1 Cell communication processes share common features that reflect a shared evolutionary history. Illustrative examples covered: • Use of chemical messengers by microbes to communicate with other nearby cells and to regulate specific pathways in response to population density (quorum sensing) • Use of pheromones to trigger reproduction and developmental pathways • Response to external signals by bacteria that influences cell movement • Epinephrine stimulation of glycogen breakdown in mammals • Temperature determination of sex in some vertebrate organisms • DNA repair mechanisms Reference: Campbell 11.1 and 11.2 Essential knowledge: 3.D.2 Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling. Illustrative examples covered: • Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells. [See also 2.D.4] • Plasmodesmata between plant cells that allow material to be transported from cell to cell • Neurotransmitters • Plant immune response • Quorum sensing in bacteria • Morphogens in embryonic development • Insulin • Human growth hormone • Thyroid hormones • Testosterone • Estrogen Reference: Campbell 11.1 and 11.2 Essential knowledge: 3.D.3. Signal transduction pathways link signal reception with cellular response. Illustrative examples covered: • G-protein linked receptors • Ligand-gated ion channels • Receptor tyrosine kinases • Ligand-gated ion channels • Second messengers, such as cyclic GMP, cyclic AMP, calcium ions (Ca2+), and inositol triphosphate (IP3) Reference: Campbell 11.3 AP Biology Cell to cell communication Page 2 Essential knowledge: 3.D.4. Changes in signal transduction pathways can alter cellular response. Illustrative examples covered: • Diabetes, heart disease, neurological disease, autoimmune disease, cancer, and cholera • Effects of neurotoxins, poisons, pesticides • Drugs (Hypertensives, Anesthetics, Antihistamines, and Birth Control Drugs) Reference: Campbell 11.3 and 11.4 Labs: 1. Introductory lab: Cell to cell with dialysis tubes filled with starch and Lygols. Case study: Insulin signaling Read the overview – Cellular messaging on page 206 of chapter 11 http://www.pbs.org/wnet/nature/lessons/survival-of-the-fastest-predators-and-prey-on-theafrican-savannah/video-segments/5662/ Cheetah vs Gazelle INTRODUCTION: The Cellular Internet Cell-to-cell communication allows the trillions of cells in a multicellular organism to communicate to coordinate their activities. Communication between cells is important for multicellular and unicellular organisms. Biologists have discovered universal mechanisms of cellular regulation involving the same small set of cell-signaling mechanisms. o The ubiquity of these mechanisms provides additional evidence for the evolutionary relatedness of all life. Cells most often communicate by chemical signals, although signals also take other forms. Cell-to-cell communication, or signaling, is an important part of understanding cell functions as well as system functions. Suggest some types of cell signaling that you have read about or learnt about: 1. neurotransmitters that are recognized in the synapse, 2. antigens triggering antibody responses, 3. and target cells responding to specific hormones. AP Biology Cell to cell communication Page 3 Concept 11.1 External signals are converted to responses within the cell Activity: Overview of Cell Signaling Mastering Biology website Cell signaling evolved early in the history of life. One topic of cell “conversation” is sex. How is this possible in yeast? . How is this advantageous to this species? How is the mating signal changed or transduced into a form that brings about the cellular response (of mating)? The molecular details of these pathways are strikingly similar in yeast and mammalian cells, even though their last common ancestor lived over a billion years ago. Signaling systems of bacteria and plants also share similarities. AP Biology Cell to cell communication Page 4 Bassler_slides quorum bacteria.ppt What is quorum sensing and why is it beneficial? Local and long distance signaling In other cases, the signaling cell secretes messenger molecules. Some transmitting cells release local regulators that influence cells in the local vicinity. Read and make some notes AP Biology Cell to cell communication Page 5 Plants and animals use hormones for long-distance signaling. AP Biology Cell to cell communication Page 6 The three stages of cell signaling are reception, transduction, and response. What happens when a cell encounters a secreted signaling molecule? AP Biology Cell to cell communication Page 7 Concept 11.2 Reception: A signal molecule binds to a receptor protein, causing it to change shape Activity: Reception The cell targeted by a particular chemical signal has a receptor protein on or in the target cell that recognizes the signal molecule. Recognition occurs when the signal binds to a specific site on the receptor that is complementary in shape to the signal. The signal molecule behaves as a ligand, a small molecule that binds with specificity to a larger molecule. Ligand binding generally causes the receptor protein to undergo a change in shape. Ligand binding may activate the receptor so that it can interact with other molecules. For other receptors, ligand binding 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. There are three major types of membrane receptors: 1. 2. 3. Study Figure 11.7: Exploring Cell- Surface Transmembrane Receptors. Pages 211 to 213. AP Biology Cell to cell communication Page 8 AP Biology Cell to cell communication Page 9 Intracellular Receptors Intracellular signal receptors are found in the cytoplasm or nucleus of target cells. Use fig 11.9 on page 214 to annotate this diagram Such chemical messengers are either hydrophobic enough or small enough to cross the phospholipid interior of the plasma membrane. AP Biology Cell to cell communication Page 10 Hydrophobic messengers include the steroid and thyroid hormones of animals. Another chemical signaling molecule with an intracellular receptor is nitric oxide (NO), a gas whose small size allows it to pass between membrane phospholipids. Testosterone is secreted by the testis and travels through the blood to enter cells throughout the body. o Only cells that contain receptor molecules for testosterone respond. o In these cells, the hormone binds and activates the receptor protein. o The activated proteins enter the nucleus and turn on specific genes that control male sex characteristics. How does the activated hormone-receptor complex turn on genes? Concept 11.3 Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell The transduction stage of signaling is usually a multistep pathway that greatly amplifies the signal. o If some molecules in a pathway transmit a signal to multiple molecules at the next step in the series, the result can be a large number of activated molecules at the end of the pathway. Activity: Signal Transduction Pathways The binding of a specific signaling molecule to a receptor in the plasma membrane triggers the first step in the chain of molecular interactions—the signal transduction pathway—that leads to a particular response within the cell. Signal transduction pathways act like falling dominoes. The signal-activated receptor activates another protein, which activates another, and so on, until the protein that produces the final cellular response is activated. The relay molecules that relay a signal from receptor to response are often proteins. o The interaction of proteins is a major theme of cell signaling. o Protein interaction is a unifying theme of all cellular regulation. The original signal molecule is not passed along the pathway and may not even enter the cell. When the signal is relayed along a pathway, information is passed on. o At each step, the signal is transduced into a different form, often by a conformational change in a protein. o The conformational change is often brought about by phosphorylation. AP Biology Cell to cell communication Page 11 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. o By dephosphorylating and thus inactivating protein kinases, phosphatases provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present. o Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to a signal. Many signaling pathways involve small, water-soluble, nonprotein molecules or ions called second messengers. o The extracellular signaling molecule that binds to the membrane receptor is a pathway’s “first messenger.” Second messengers diffuse rapidly throughout the cell. Second messengers participate in pathways initiated by both G-protein-linked receptors and tyrosine-kinase receptors. o Two of the most widely used second messengers are cyclic AMP and Ca2+. o A large variety of relay proteins are sensitive to the cytosolic concentration of one or the other of these second messengers. Epinephrine causes glycogen breakdown without entering the cell. How is this possible? Certain microbes cause disease by disrupting G-protein signaling pathways. For example, the cholera bacterium, Vibrio cholerae, may be present in water contaminated with human feces. This bacterium colonizes the small intestine and produces a toxin that modifies a G protein that regulates salt and water secretion. The modified G protein is unable to hydrolyze GTP to GDP and remains stuck in its active form, continuously stimulating adenylyl cyclase to make cAMP. AP Biology Cell to cell communication Page 12 The resulting high concentration of cAMP causes the intestinal cells to secrete large amounts of water and salts into the intestines, leading to profuse diarrhea and possible death from loss of water and salts. Treatments for certain human conditions involve signaling pathways. One pathway uses cyclic GMP, or cGMP, as a signaling molecule. Its effects include the relaxation of smooth muscle cells in artery walls. A compound was developed to treat chest pains. This compound inhibits the hydrolysis of cGMP to GMP, prolonging the signal and increasing blood flow to the heart muscle. Under the trade name Viagra, this compound is now widely used as a treatment for erectile dysfunction. Viagra causes dilation of blood vessels, allowing increased blood flow to the penis. Many signaling molecules in animals, including neurotransmitters, growth factors, and some hormones, induce responses in their target cells via signal transduction pathways that increase the cytosolic concentration of Ca2+. Calcium is even more widely used than cAMP as a second messenger. ○ In animal cells, increases in Ca2+ concentrations may cause contraction of muscle cells, secretion of certain substances, and cell division. In plant cells, increases in Ca2+ trigger responses such as the pathway for greening in response to light. AP Biology Cell to cell communication Page 13 Concept 11.4 Response: Cell signaling leads to regulation of cytoplasmic activities or transcription Activity: Cellular Responses Activity: Build a Signaling Pathway Ultimately, a signal transduction pathway leads to the regulation of one or more cellular activities. The response may occur in the nucleus or the cytoplasm. Many signaling pathways ultimately regulate protein synthesis, usually by turning specific genes on or off in the nucleus. Like an activated steroid receptor, the final activated molecule in a signaling pathway may function as a transcription factor. Often a transcription factor regulates several different genes. Signaling pathways may regulate the activity of proteins rather than their synthesis, directly affecting proteins that function outside of the nucleus. A signal may cause the opening or closing of an ion channel or a change in cell metabolism. For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen. The Specificity of cell signaling Create a short note to explain specificity and the diagram above. AP Biology Cell to cell communication Page 14 Different pathways may have some molecules in common. Cells may use the same receptor protein, but differences in other proteins lead to different responses. Cells may use differing receptor proteins for the same signaling molecule, leading to different responses. The importance of relay proteins that serve as branch or intersection points in signaling pathways is underscored when these proteins are defective or missing. Explain the cause and symptoms of the inherited disorder Wiskott-Aldrich syndrome (WAS) AP Biology Cell to cell communication Page 15