AP Biology
Cell Communication AP Biology The “Cellular Internet” • Biologists have discovered some universal mechanisms of cellular regulation that involve cell-to-cell communication. •External signals are converted into responses within the cell Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Cell Signaling • Yeast cells – Identify their mates by cell signaling 1 Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 2 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. factor Receptor a Yeast cell, factor Yeast cell, mating type a mating type a 3 New a/ cell. Figure 11.2 The nucleus of the fused cell includes all the genes from the a and a cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings a/ Methods used by Cells to Communicate • Cell-Cell communication • Cell Signaling using chemical messengers 1. Local signaling over short distances • Cell-Cell Recognition • Local regulators – Paracrine (growth factors) – Synaptic (neurotransmitters) 2. Long distance signaling • Hormones Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell-Cell Communication • Animal and plant cells – Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell-Cell Communication Animal cells use gap junctions to send signals Cells must be in direct contact Protein channels connecting two adjoining cells Gap junctions between animal cells AP Biology Cell-Cell Communication Plant cells use plasmodesmata to send signals Cells must be in direct contact Gaps in the cell wall connecting the two adjoining cells together Plasmodesmata between plant cells AP Biology Local Signaling: Cell-Cell Recognition • In local signaling, animal cells may communicate via direct contact • Membrane bound cell surface molecules • Glycoproteins • Glyolipids Figure 11.3(b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local Signaling: Local Regulators • In other cases, animal cells – Communicate using local regulators – Only work over a short distance Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Long-distance Signaling: Hormones • In long-distance signaling – Both plants and animals use hormones Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell Figure 11.4 (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all C body cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Long-Distance Signaling Nervous System in Animals Electrical signals through neurons Endocrine System in Animals Uses hormones to transmit messages over long distances Plants also use hormones Some transported through vascular system Others are released into the air AP Biology The Three Stages of Cell Signaling • Earl W. Sutherland (1971) – Discovered how the hormone epinephrine acts on cells • Sutherland suggested that cells receiving signals went through three processes – Reception – Transduction – Response • Called Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three Stages of Cell Signaling EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception Receptor The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!) Signaling molecule Signaling molecule binds to the receptor protein AP Biology Three Stages of Cell Signaling CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction Receptor 2nd Messenger! Relay molecules in a signal transduction pathway Signaling molecule The signal is converted into a form that can produce a cellular response AP Biology Three Stages of Cell Signaling CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Can be catalysis, activation of a gene, triggering apoptosis, almost anything! The transduced signal triggers a cellular response AP Biology Signal Transduction Animation http://media.pearsoncmg.com/bc/bc_ campbell_biology_7/media/interactiv emedia/activities/load.html?11&A http://www.wiley.com/legacy/college/bo yer/0470003790/animations/signal_tran sduction/signal_transduction.htm AP Biology There are three most common types of membrane receptor proteins. G-protein coupled receptors Receptor tyrosine-kinases Ion channel receptors AP Biology 1. Reception • A signal molecule, a ligand, binds to a receptor protein in a lock and key fashion, causing the receptor to change shape. Most receptor proteins are in the cell membrane but some are inside the cell. The G-protein is a common membrane receptor. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G-Protein Coupled Receptors are often involved in diseases such as bacterial infections. G-Protein Receptors Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule Enzyme GDP 2 1 CYTOPLASM G protein (inactive) GDP GTP Activated enzyme i GTP GDP P 4 3 Cellular response AP Biology Inactive enzyme • Receptor tyrosine kinases Signal-binding site Signal molecule Signal molecule Helix in the Membrane Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Tyr Dimer Activated relay proteins Figure 11.7 Tyr P Tyr P Tyr Tyr P Tyr P Tyr P Tyr Tyr P Tyr Tyr Tyr Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine-kinase (phosphorylated dimer) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings P Tyr P Tyr P Tyr Tyr P Tyr P Tyr P Inactive relay proteins Cellular response 1 Cellular response 2 Ion Channel Receptors Very important in 1 Gate closed Ions Signaling molecule (ligand) the nervous system Signal triggers the opening of an ion channel depolarization Triggered by neurotransmitters Ligand-gated ion channel receptor Plasma membrane 2 Gate open AP Biology Cellular response 3 Gate closed 2. Transduction • Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways – Can amplify a signal (Amplifies the signal by activating multiple copies of the next component in the pathway) – Provide more opportunities for coordination and regulation • At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fig. 11-9 Signaling molecule Receptor Transduction: Activated relay molecule Inactive protein kinase 1 A Phosphorylation Cascade Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 Pi ATP ADP Active protein kinase 3 PP Inactive protein P ATP P ADP AP Biology Pi PP Active protein Cellular response Protein Phosphorylation and Dephosphorylation • Many signal pathways – Include phosphorylation cascades – In this process, a series of protein kinases add a phosphate to the next one in line, activating it – Phosphatase enzymes then remove the phosphates Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • A phosphorylation cascade Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 1 A relay molecule activates protein kinase 1. 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 1 Inactive protein kinase 2 ATP Pi PP Inactive protein kinase 3 5 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. Figure 11.8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings P Active protein kinase 2 ADP 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. ATP ADP Pi Active protein kinase 3 PP Inactive protein P 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP ADP Pi PP P Active protein Cellular response The transduction stage of signaling is often a multistep process that amplifies the signal. About 1% of our genes are thought to code for kinases. http://media.pearsoncmg.com/bc /bc_campbell_biology_7/media/in teractivemedia/activities/load.ht ml?11&C AP Biology Small Molecules and Ions as Second Messengers • Secondary messengers – Are small, nonprotein, water-soluble molecules or ions that act as secondary messengers. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP • Many G-proteins trigger the formation of cAMP, which then acts as a second messenger in cellular pathways. First messenger (signal molecule such as epinephrine) G protein G-protein-linked receptor Adenylyl cyclase GTP ATP cAMP Protein kinase A Cellular responses Figure 11.10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP • Cyclic AMP (cAMP) – Is made from ATP NH2 N N O O O N N – O P O P O P O Ch2 O O O NH2 NH2 O Pyrophosphate P Pi O CH2 Phoshodiesterase ATP Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings O OH Cyclic AMP N N O HO P O CH2 O O P O N N N N Adenylyl cyclase O OH OH N N O H2O OH OH AMP Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP Transduction in a G-protein pathway Second messenger Protein kinase A Cellular responses AP Biology Calcium ions and Inositol Triphosphate (IP3) • Calcium, when released into the cytosol of a cell acts as a second messenger in many different pathways Calcium is an important EXTRACELLULAR FLUID ATP Plasma membrane Ca2+ pump Mitochondrion second messenger because cells are able to regulate its concentration in the cytosol Nucleus CYTOSOL Ca2+ pump ATP Key Ca2+ pump Endoplasmic reticulum (ER) High [Ca2+] Low [Ca2+] Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other second messengers such as inositol triphosphate and diacylglycerol can trigger an increase in calcium in the cytosol 1 A signal molecule binds 2 Phospholipase C cleaves a to a receptor, leading to plasma membrane phospholipid activation of phospholipase C. called PIP2 into DAG and IP3. EXTRACELLULAR FLUID 3 DAG functions as a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP PIP2 G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Ca2+ Cellular response Ca2+ (second messenger) Figure 11.12 4 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol. 6 The calcium ions activate the next protein in one or more signaling pathways. Growth factor 3. Response Receptor Reception Many possible outcomes This example shows a transcription response Phosphorylation cascade CYTOPLASM Inactive transcription factor Active transcription factor P DNA Gene NUCLEUS mRNA AP Biology Transduction Response Signaling molecule Specificity of the Receptor signal The same signal molecule can trigger different responses Many responses can come from one signal! Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads Cell B. Pathway branches, to a single response. leading to two responses. AP Biology The signal can also trigger an activator or inhibitor The signal can also trigger multiple receptors and different responses Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs Cell D. Different receptor between two pathways. leads to a different response. AP Biology Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities. AP Biology Long-distance Signaling Intracellular signaling includes hormones that are hydrophobic and can cross the cell membrane. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. Testosterone acts as a transcription factor. AP Biology • Steroid hormones – Bind to intracellular receptors Hormone EXTRACELLULAR (testosterone) FLUID 1 The steroid hormone testosterone passes through the plasma membrane. Plasma membrane Receptor protein Hormonereceptor complex 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. 3 The hormone- DNA receptor complex enters the nucleus and binds to specific genes. mRNA 4 The bound protein NUCLEUS stimulates the transcription of the gene into mRNA. New protein 5 The mRNA is Figure 11.6 CYTOPLASM Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings translated into a specific protein. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins – Can increase the signal transduction efficiency Signal molecule Plasma membrane Receptor Scaffolding protein Figure 11.16 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Three different protein kinases Termination of the Signal • Signal response is terminated quickly – By the reversal of ligand binding Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Any Questions?? Can You Hear Me Now? AP Biology Two systems control all physiological processes 1. Nervous System – neurosecretory glands in endocrine tissues secrete hormones. 2. Endocrine System AP Biology Human Endocrine System AP Biology Major Vertebrate Endocrine Glands Their Hormones (Hypothalamus–Parathyroid glands) AP Biology AP Biology Figure 45.6b Hormones of the hypothalamus and pituitary glands Neurosecretory cells in endocrine organs and tissues secrete hormones. These hormones are excreted AP Biology into the circulatory system. Stress and the Adrenal Gland AP Biology http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/site s/dl/free/0072437316/120109/bio48.swf::Action%20of% 20Epinephrine%20on%20a%20Liver%20Cell Figure 45.4 One chemical signal, different effects AP Biology Figure 45.9 Hormonal control of calcium homeostasis in mammals http://bcs.whfreeman.co m/thelifewire/content/ch p42/4202003.html AP Biology Figure 45.10 Glucose homeostasis maintained by insulin and glucagon http://vcell.ndsu.nodak.edu/animations/regulatedsecre AP Biology tion/movie.htm Cellular Communication Review Denise Green AP Biology REVIEW: Signal-transduction pathway Definition: Signal on a cell’s surface is converted into a specific cellular response Local signaling (short distance): √ Paracrine (growth factors) √ Synaptic (neurotransmitters) Long distance: hormones AP Biology Stages of cell signaling Sutherland (‘71) Glycogen depolymerization by epinephrine 3 steps: •Reception: target cell detection •Transduction: single-step or series of changes •Response: triggering of a specific cellular response AP Biology • G-protein-linked receptors Signal-binding site Segment that interacts with G proteins G-protein-linked Receptor Plasma Membrane Activated Receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP Pi Figure 11.7 Cellular response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inctivate enzyme Protein phosphorylation Protein activity AP Biology regulation Adding phosphate from ATP to a protein (activates proteins) Enzyme: protein kinases (1% of all our genes) Example: cell reproduction Reversal enzyme: protein phosphatases Second messengers Non-protein signaling pathway Example: cyclic AMP (cAMP) Ex: Glycogen breakdown with epinephrine Enzyme: adenylyl cyclase G-protein-linked receptor in membrane (guanosine di- or triphosphate) AP Biology Cellular responses to signals Cytoplasmic activity regulation Cell metabolism regulation Nuclear transcription regulation AP Biology 2010 Free Response Question AP Biology The three stage of cellular signaling: Reception, Transduction, and Response. http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A AP Biology
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