Chapter 11 Cell Communication Dr. Wendy Sera Houston Community College Biology 1406 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. 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 1
Figure 11.1 How does cell signaling trigger the desperate flight of this impala? Epinephrine 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 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 2
1 Exchange of mating factors Receptor a α factor 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 Evolution of Cell Signaling, cont. athway 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. 1 Individual rod-shaped cells Figure 11.3 Communication among bacteria 0.5 mm 2 2 Aggregation in progress 3 Spore-forming structure (fruiting body) 2.5 mm Fruiting bodies 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 lasma membranes Cell wall Gap junctions between animal cells lasmodesmata between plant cells (a) Cell junctions Figure 11.4 Communication by direct contact between cells (b) Cell-cell recognition 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 4
Local signaling Target cells Secreting cell Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Secretory vesicles Local regulator Target cell (a) aracrine signaling (b) Synaptic signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel (c) Endocrine (hormonal) signaling Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals 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 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 5
Local signaling Target cells Secreting cell Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Secretory vesicles Local regulator Target cell (a) aracrine signaling (b) Synaptic signaling Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel (c) Endocrine (hormonal) signaling Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals The Three Stages of Cell Signaling: A review Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response Figure 11.6 Overview of cell signaling EXTRACELLULAR FLUID lasma membrane CYTOLASM Receptor 1 Reception 2 Transduction 1 2 3 Relay molecules 3 Response Activation of cellular response Signaling molecule 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 Animation: Overview of Cell Signaling 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 7
Receptors in the lasma 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 Receptors: G rotein-coupled Receptors G protein-coupled receptors (GCRs) are cell surface transmembrane receptors that work with the help of a G protein G proteins bind the energy-rich GT G proteins are all very similar in structure GCR systems are extremely widespread and diverse in their functions 60% of all medicines work by affecting G-protein pathways! Bacterial infections: Cholera, ertusis, Botulism caused by toxins affecting G-protein function. Figure 11.8a Exploring cell-surface transmembrane receptors Signaling molecule binding site Segment that interacts with G proteins G protein-coupled receptor 8
Figure 11.8 Exploring cell-surface transmembrane receptors G protein-coupled receptor lasma membrane Activated receptor Signaling molecule enzyme CYTOLASM GD G protein (inactive) Enzyme 1 2 GD GT GD GT Activated enzyme GT GD i Cellular response 3 4 Receptors: Receptor osine 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 Figure 11.8 Exploring cell-surface transmembrane receptors Signaling molecule Signaling molecule (ligand) Ligand-binding site helix in the membrane osines Receptor tyrosine kinase proteins CYTOLASM (inactive monomers) 1 2 Dimer Activated relay proteins Activated tyrosine kinase regions (unphosphorylated dimer) 6 AT 6 AD Fully activated receptor tyrosine kinase (phosphorylated dimer) relay proteins Cellular response 1 Cellular response 2 3 4 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 Ca 2+, 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. Figure 11.8 Exploring cell-surface transmembrane receptors 1 Signaling molecule (ligand) Gate closed Ions 2 Gate open Ligand-gated ion channel receptor lasma membrane Cellular response 3 Gate closed 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 10
Figure 11.9 Steroid hormone interacting with an intracellular receptor Hormone (aldosterone) Receptor protein EXTRA- CELLULAR FLUID lasma membrane Hormonereceptor complex mrna NUCLEUS DNA New protein CYTOLASM 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 Signal Transduction athways 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 11
rotein hosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a phosphorylation cascade rotein kinases transfer phosphates from AT to protein, a process called phosphorylation rotein 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 Signaling molecule Receptor protein kinase 1 Activated relay molecule Active protein kinase 1 Figure 11.10 A phosphorylation cascade protein kinase AT 2 AD i Active protein kinase 2 protein kinase AT 3 AD i Active protein kinase 3 protein AT AD i Active protein Cellular response 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 GCRs and RTKs Cyclic AM and calcium ions are common second messengers 12
Cyclic AM Cyclic AM (cam) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts AT to cam in response to an extracellular signal Figure 11.11 Cyclic AM Adenylyl cyclase yrophosphate AT cam Cyclic AM, cont. Many signal molecules trigger formation of cam Other components of cam pathways are G proteins, G protein-coupled receptors, and protein kinases cam 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 13
First messenger (signaling molecule such as epinephrine) G protein Adenylyl cyclase GT G protein-coupled receptor AT cam Second messenger Figure 11.12 cam as a second messenger in a G protein signaling pathway rotein kinase A Cellular responses Calcium Ions Calcium ions (Ca 2+ ) act as a second messenger in many pathways Ca 2+ 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 Endoplasmic reticulum (ER) AT lasma membrane Mitochondrion Nucleus Ca 2+ pump EXTRACELLULAR FLUID CYTOSOL AT AT Key High [Ca 2+ ] Low [Ca 2+ ] 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 athways leading to the release of calcium involve inositol triphosphate (I 3 ) and diacylglycerol (DAG) as additional second messengers These two are produced by cleavage of a certain phospholipid in the plasma membrane Figure 11.14 Calcium and I 3 in signaling pathways EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein CYTOSOL Endoplasmic reticulum (ER) lumen Nucleus G protein-coupled receptor GT I 3 -gated calcium channel Ca 2+ Ca 2+ (second messenger) hospholipase C Various proteins activated I 2 DAG I 3 (second messenger) Cellular responses Animation: Signal Transduction athways 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) 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 Figure 11.15 Nuclear responses to a signal: the activation of a specific gene by a growth factor CYTOLASM Growth factor Receptor hosphorylation cascade Reception Transduction transcription factor Active transcription factor Response DNA Gene NUCLEUS mrna 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 Figure 11.16 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine (adrenaline) Reception Transduction Binding of epinephrine to G protein-coupled receptor G protein (1 molecule) Active G protein (10 2 molecules) adenylyl cyclase Active adenylyl cyclase (10 2 ) AT Cyclic AM (10 4 ) protein kinase A Active protein kinase A (10 4 ) Response Glycogen Glucose 1-phosphate (10 8 molecules) phosphorylase kinase Active phosphorylase kinase (10 5 ) glycogen phosphorylase Active glycogen phosphorylase (10 6 ) 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 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 Figure 11.19 Apoptosis of a human white blood cell 2 µm Apoptotic athways 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 18
Apoptotic athways, 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, arkinson s and Alzheimer s); interference with apoptosis may contribute to some cancers Figure 11.21 Effect of apoptosis during paw development in the mouse Interdigital tissue Cells undergoing apoptosis 1 mm Space between digits 19