Chapter 11 Cell Communication Dr. Wendy Sera Houston Community College Biology 1406 © 2014 Pearson Education, Inc. Key Concepts in Chapter 11 1. External signals are converted to responses within the cell. 2. Reception: A signaling molecule binds to a receptor protein, causing it to change shape. 3. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell. 4. Response: Cell signaling leads to regulation of transcription or cytoplasmic activities. 5. Apoptosis integrates multiple cell-signaling pathways. © 2014 Pearson Education, Inc. Cellular Messaging Cell-to-cell communication is essential for multicellular organisms Cells can signal to each other and interpret the signals they receive from other cells and the environment The same small set of cell signaling mechanisms shows up in diverse species and processes Cells most often communicate with each other via chemical signals For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine © 2014 Pearson Education, Inc. 1 Figure 11.1—How does cell signaling trigger the desperate flight of this impala? Epinephrine © 2014 Pearson Education, Inc. Concept 11.1: External signals are converted to responses within the cell Communication among microorganisms provides some insight into how cells send, receive, and respond to signals A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response © 2014 Pearson Education, Inc. Evolution of Cell Signaling The yeast, Saccharomyces cerevisiae, has two mating types, a and Cells of different mating types locate each other via secreted factors specific to each type Signal transduction pathways convert signals received at a cell’s surface into cellular responses The molecular details of signal transduction in yeast and mammals are strikingly similar © 2014 Pearson Education, Inc. 2 α factor Receptor 1 Exchange of mating factors a α Yeast cell, a factor Yeast cell, mating type a mating type α 2 Mating a α 3 New a/ cell a/ α Figure 11.2— Communication between mating yeast cells © 2014 Pearson Education, Inc. Evolution of Cell Signaling, cont. Pathway similarities suggest that ancestral signaling molecules that evolved in prokaryotes and singlecelled eukaryotes were adopted for use in their multicellular descendants Example: The concentration of signaling molecules allows the soil-dwelling myxobacteria (“slime bacteria”) to share information about nutrient availability. When food is scarce, starving cells secrete a molecule that reaches neighboring cells and stimulates them to aggregate and produce fruiting bodies that produces spores that can survive harsh conditions. © 2014 Pearson Education, Inc. Figure 11.3— Communication among bacteria 1 Individual rod-shaped cells 2 2 Aggregation in progress 0.5 mm 3 Spore-forming structure (fruiting body) 2.5 mm Fruiting bodies © 2014 Pearson Education, Inc. 3 Local and Long-Distance Signaling Cells in a multicellular organism communicate via signaling molecules. Two types of signaling: 1) local signaling and 2) long-distance signaling In local signaling, animal cells may communicate by direct contact Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells Signaling substances in the cytosol can pass freely between adjacent cells © 2014 Pearson Education, Inc. Plasma membranes Gap junctions between animal cells Cell wall Plasmodesmata between plant cells (a) Cell junctions Figure 11.4— Communication by direct contact between cells (b) Cell-cell recognition © 2014 Pearson Education, Inc. Local Signaling, cont. In many other cases, animal cells communicate using secreted messenger molecules that travel only short distances Growth factors, which stimulate nearby target cells to grow and divide, are one class of such local regulators in animals This type of local signaling in animals is called paracrine signaling © 2014 Pearson Education, Inc. 4 Local signaling Electrical signal triggers release of neurotransmitter. Target cells Neurotransmitter diffuses across synapse. Secreting cell Secretory vesicles Target cell Local regulator (a) Paracrine signaling (b) Synaptic signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel Figure 11.5—Local and long-distance cell signaling by secreted molecules in animals (c) Endocrine (hormonal) signaling © 2014 Pearson Education, Inc. Local Signaling, cont. Synaptic signaling occurs in the animal nervous system when a neurotransmitter is released in response to an electric signal Local signaling in plants is not well understood beyond communication between plasmodesmata © 2014 Pearson Education, Inc. Long-Distance Signaling In long-distance signaling, plants and animals use chemicals called hormones Hormonal signaling in animals is called endocrine signaling; specialized cells release hormones, which travel to target cells via the circulatory system The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal © 2014 Pearson Education, Inc. 5 Local signaling Electrical signal triggers release of neurotransmitter. Target cells Neurotransmitter diffuses across synapse. Secreting cell Secretory vesicles Target cell Local regulator (b) Synaptic signaling (a) Paracrine signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Figure 11.5—Local and long-distance cell signaling by secreted molecules in animals Hormone travels in bloodstream. Blood vessel (c) Endocrine (hormonal) signaling © 2014 Pearson Education, Inc. The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response © 2014 Pearson Education, Inc. Figure 11.6—Overview of cell signaling EXTRACELLULAR FLUID 1 CYTOPLASM Plasma membrane Reception 2 Transduction 3 Response Receptor 1 2 Relay molecules 3 Activation of cellular response Signaling molecule © 2014 Pearson Education, Inc. 6 The Three Stages of Cell Signaling, cont. In reception, the target cell detects a signaling molecule that binds to a receptor protein on the cell surface In transduction, the binding of the signaling molecule alters the receptor and initiates a signal transduction pathway; transduction often occurs in a series of steps In response, the transduced signal triggers a specific response in the target cell © 2014 Pearson Education, Inc. Animation: Overview of Cell Signaling © 2014 Pearson Education, Inc. Concept 11.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins © 2014 Pearson Education, Inc. 7 Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane There are three main types of membrane receptors: 1. G protein-coupled receptors (largest family of cell-surface receptors) 2. Receptor tyrosine kinases 3. Ion channel receptors © 2014 Pearson Education, Inc. Receptors: G Protein-coupled Receptors G protein-coupled receptors (GPCRs) are cell surface transmembrane receptors that work with the help of a G protein G proteins bind the energy-rich GTP G proteins are all very similar in structure GPCR systems are extremely widespread and diverse in their functions 60% of all medicines work by affecting G-protein pathways! Bacterial infections: Cholera, Pertusis, Botulism caused by toxins affecting G-protein function. © 2014 Pearson Education, Inc. Figure 11.8a—Exploring cell-surface transmembrane receptors Signaling molecule binding site Segment that interacts with G proteins G protein-coupled receptor © 2014 Pearson Education, Inc. 8 Figure 11.8—Exploring cell-surface transmembrane receptors G protein-coupled receptor Plasma membrane Inactive enzyme GTP GDP GDP G protein (inactive) CYTOPLASM Signaling molecule Activated receptor GTP GDP Enzyme 2 1 Activated enzyme GTP GDP Pi Cellular response 4 3 © 2014 Pearson Education, Inc. Receptors: Receptor Tyrosine Kinases Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers © 2014 Pearson Education, Inc. Figure 11.8—Exploring cell-surface transmembrane receptors Signaling molecule (ligand) helix in the Signaling molecule Ligand-binding site membrane Tyrosines CYTOPLASM Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) Dimer 2 1 Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr P Tyr 6 ATP Activated tyrosine kinase regions (unphosphorylated dimer) 3 6 ADP P Tyr P Tyr Tyr P Tyr P Tyr P Fully activated receptor tyrosine kinase (phosphorylated dimer) P Tyr Tyr P P Tyr P Tyr Tyr P Tyr P Cellular response 1 Cellular response 2 Inactive relay proteins 4 © 2014 Pearson Education, Inc. 9 Receptors: Ligand-gated Ion Channel A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Very important in nervous system function— neurotransmitters are bind as ligands to ion channels on the receiving neuron, causing the channel to open. © 2014 Pearson Education, Inc. Figure 11.8—Exploring cell-surface transmembrane receptors 1 Signaling molecule (ligand) Gate closed Ligand-gated ion channel receptor 3 2 Ions Gate open Cellular response Plasma membrane Gate closed © 2014 Pearson Education, Inc. Intracellular Receptors Intracellular receptor proteins are found in the cytoplasm or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes © 2014 Pearson Education, Inc. 10 Hormone (aldosterone) Figure 11.9— Steroid hormone interacting with an intracellular receptor EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA New protein NUCLEUS CYTOPLASM © 2014 Pearson Education, Inc. Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps Multistep pathways can greatly amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response © 2014 Pearson Education, Inc. Signal Transduction Pathways The binding of a signaling molecule to a receptor triggers the first step in a chain of molecular interactions Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein © 2014 Pearson Education, Inc. 11 Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a phosphorylation cascade Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Protein phosphatases rapidly remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required © 2014 Pearson Education, Inc. Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Figure 11.10—A phosphorylation cascade Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response © 2014 Pearson Education, Inc. Small Molecules and Ions as Second Messengers The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by GPCRs and RTKs Cyclic AMP and calcium ions are common second messengers © 2014 Pearson Education, Inc. 12 Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal © 2014 Pearson Education, Inc. Figure 11.11—Cyclic AMP Adenylyl cyclase Pyrophosphate ATP cAMP © 2014 Pearson Education, Inc. Cyclic AMP, cont. Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase © 2014 Pearson Education, Inc. 13 First messenger (signaling molecule such as epinephrine) Adenylyl cyclase G protein GTP G protein-coupled receptor ATP cAMP Second messenger Protein kinase A Figure 11.12—cAMP as a second messenger in a G protein signaling pathway Cellular responses © 2014 Pearson Education, Inc. Calcium Ions Calcium ions (Ca2+) act as a second messenger in many pathways Ca2+ can function as a second messenger because its concentration in the cytosol is normally much lower than the concentration outside the cell A small change in number of calcium ions thus represents a relatively large percentage change in calcium concentration © 2014 Pearson Education, Inc. Endoplasmic reticulum (ER) Plasma membrane ATP Mitochondrion Nucleus Ca2+ pump ATP CYTOSOL ATP EXTRACELLULAR FLUID Key © 2014 Pearson Education, Inc. High [Ca2+] Low [Ca2+] Figure 11.13—The maintenance of calcium ion concentrations in an animal cell 14 Calcium Ions, cont. A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers These two are produced by cleavage of a certain phospholipid in the plasma membrane © 2014 Pearson Education, Inc. Figure 11.14—Calcium and IP3 in signaling pathways Signaling molecule (first messenger) G protein EXTRACELLULAR FLUID GTP CYTOSOL G protein-coupled receptor Endoplasmic reticulum (ER) lumen DAG Phospholipase C IP3-gated calcium channel Ca2+ Nucleus Ca2+ (second messenger) PIP2 IP3 (second messenger) Various proteins activated Cellular responses © 2014 Pearson Education, Inc. Animation: Signal Transduction Pathways © 2014 Pearson Education, Inc. 15 Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities The cell’s response to an extracellular signal is called the “output response” Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm (cytoplasmic responses) or in the nucleus (nuclear responses) © 2014 Pearson Education, Inc. Nuclear Response Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor © 2014 Pearson Education, Inc. Figure 11.15— Nuclear responses to a signal: the activation of a specific gene by a growth factor Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA © 2014 Pearson Education, Inc. 16 Cytoplasmic Responses Other pathways regulate the activity of enzymes rather than their synthesis For example, a signal could cause opening or closing of an ion channel in the plasma membrane, or a change in cell metabolism Signaling pathways can also affect the overall behavior of a cell, for example, a signal could lead to cell division © 2014 Pearson Education, Inc. Figure 11.16—Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine (adrenaline) Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (10 4) Inactive phosphorylase kinase Response Active phosphorylase kinase (105) Glycogen Inactive glycogen phosphorylase Glucose 1-phosphate (108 molecules) Active glycogen phosphorylase (106) © 2014 Pearson Education, Inc. Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling If ligand concentration falls, fewer receptors will be bound Unbound receptors revert to an inactive state © 2014 Pearson Education, Inc. 17 Concept 11.5: Apoptosis integrates multiple cell-signaling pathways Cells that are infected or damaged or have reached the end of their functional lives often undergo “programmed cell death” Apoptosis is the best understood type Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2014 Pearson Education, Inc. Figure 11.19—Apoptosis of a human white blood cell 2 µm © 2014 Pearson Education, Inc. Apoptotic Pathways and the Signals That Trigger Them In humans and other mammals, several different pathways, including about 15 caspases, can carry out apoptosis Caspases are the main proteases—enzymes that cut up proteins Apoptosis can be triggered by signals from outside the cell or inside it, such as: 1. An extracellular death-signaling ligand 2. Irreparable DNA damage in the nucleus 3. Excessive protein misfolding in the ER © 2014 Pearson Education, Inc. 18 Apoptotic Pathways, cont. Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals For example, apoptosis is a normal part of embryonic development of hands and feet in humans (and paws in other mammals) Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers © 2014 Pearson Education, Inc. Figure 11.21—Effect of apoptosis during paw development in the mouse Interdigital tissue Cells undergoing apoptosis 1 mm Space between digits © 2014 Pearson Education, Inc. 19
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