Chapter 11 Cell Communication PowerPoint? Lecture Presentations for } Biology | Eighth Edition Neil Campbell and Jane Recee Overview: The Cellular Internet * Cell-to-cell communication is essential for multicellular organisms * Biologists have discovered some universal mechanisms of cellular regulation * The combined effects of multiple signals determine cell response + For example, the dilation of blood vessels is controlled by multiple moleculesConcept 11.1: External signals are converted to responses within the cell * Microbes are a window on the role of cell signaling in the evolution of lifeEvolution of Cell Signaling « Asignal transduction pathway is a series of steps by which a signal on a cell's surface is converted into a specific cellular response * Signal transduction pathways convert signals on a cell's surface into cellular responses rig te R i gitimtor eceptor SUK aN oe @Exchange e of mating factors a7 a factor Yeast cell, Yeast cell, mating type a mating type a © mating ONewala cell+ Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes * The concentration of signaling molecules allows bacteria to detect population density ryt @ Individual rod- shaped cells = @ Aggregation in process © Spore-forming structure (fruiting body) Fruiting bodiesLocal and Long-Distance Signaling * Cells in a multicellular organism communicate by chemical messengers + Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells * In local signaling, animal cells may communicate by direct contact, or cell-cell recognition rig te Gap junctions Plasmodesmata between animal cells between plant cells {a) Cell junctions (b) Cell-cell recognition* In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances * In long-distance signaling, plants and animals use chemicals called hormones Long stance signaling NE apa Torgdt cal te stimlated {a) Paracine signaling (©) Synaptic signating (6) Hormonal signalingrig tsa Local signaling (a) Paracrine signaling (b) Synaptic signaling Long-distance signaling in bloodstream to target cells {c) Hormonal signaling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rig sre CYTOPLASM Plasma membrane @ Reception Q Transduction Pig 19 -@-6- 7 Relay molecules in a signal transduction pathway CYTOPLASM Plasma membrane @ Reception @Q Transduction @Response| —@-E-o- Relay molecules in a signal transduction pathway Activation of cellular responseConcept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape * The binding between a signal molecule (ligand) and receptor is highly specific + Ashape change in a receptor is often the initial transduction of the signal * Most signal receptors are plasma membrane proteins Receptors in the Plasma Membrane * Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane * There are three main types of membrane receptors: — G protein-coupled receptors — Receptor tyrosine kinases — lon channel receptors- AG protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein * The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive a = i == — G protein-coupled receptorcig see Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at onceHg. WIC 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?*, through a channel in the receptorIntracellular Receptors « Some receptor proteins are intracellular, found in the cytosol 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rig teerig hes rig 10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 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 Pathways * The molecules that relay a signal from receptor to response are mostly proteins + Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated « Ateach step, the signal is transduced into a different form, usually a shape change in a protein Protein Phosphorylation and Dephosphorylation * In many pathways, the signal is transmitted by a cascade of protein phosphorylations + Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation* Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation * This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off rig ty "WS ADP 2D pea) cater ae # fee © ret iy? | protein in?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 G protein-coupled receptors and receptor tyrosine kinases * Cyclic AMP and calcium ions are common second m essengers 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rig. eww OH OH + 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rig ett Calcium Ions and Inositol Triphosphate (IP) * Calcium ions (Ca?*) act as a second messenger in many pathways * Calcium is an important second messenger because cells can regulate its concentrationrig. 12 High [cay « Asignal 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rig tse G protein-coupled receptor Phospholipase C iP; (second messenger) IP;-gated calcium channel CYTOSOL rig ttsto%e G protein-coupled rapod Phospholipase C IP, (second messenger) IP,-gated calcium channel~ ooo Phospholipase c —PIP2 IP; (second messenger) IP,-gated calcium channel 0? Various —* cetular 2 9 0 —> proteins —> responses (second CYTOSOL messenger ) Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities + The cell’s response to an extracellular signal is sometimes called the “output response”Nuclear and Cytoplasmic Responses * Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities * The response may occur in the cytoplasm or may involve action in the nucleus * 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 may function as a transcription factor ‘Transduction* Other pathways regulate the activity of enzymes* Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape Fig 11-16 Wild-type (shmoos) Fuss ‘forminWild-type (shmoos) AFus3 Aformin rig stiw Mating Shmoo projection w factor’ protein-coupled forming. y receptor ee ‘subunit ‘Microfilament 8Fine-Tuning of the Response « Multistep pathways have two important benefits: — Amplifying the signal (and thus the response) — Contributing to the specificity of the response Signal Amplification + Enzyme cascades amplify the cell’s response * Ateach step, the number of activated products is much greater than in the preceding stepThe Specificity of Cell Signaling and Coordination of the Response + Different kinds of cells have different collections of proteins * These different proteins allow cells to detect and respond to different signals « Even the same signal can have different effects in cells with different proteins and pathways + Pathway branching and “cross-talk” further help the cell coordinate incoming signalsey tei i | Q Relay L \ molecules DP @ 1 \ Response 1 Response 2 Response 3 Cell A. Pathway leads Cell B. Pathway branches, to a single response. leading to two responses. rye 1 1 9 | — a 1 Activation (grt. v 1 Response 4 Response 5 Cell C. Cross-talk occurs Cell D. Different receptor between two pathways. leads to a different response.Signaling Efficiency: Scaffolding Proteins and Signaling Complexes * Scaffolding proteins are large relay proteins to which other relay proteins are attached * Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathwayTermination of the Signal + Inactivation mechanisms are an essential aspect of cell signaling + When signal molecules leave the receptor, the receptor reverts to its inactive state Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways * Apoptosis is programmed or controlled cell suicide * Acell is chopped and packaged into vesicles that are digested by scavenger cells + Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cellsApoptosis in the Soil Worm Caenorhabditis elegans * Apoptosis is important in shaping an organism during embryonic development * The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans * In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosisrig shew rig teva protein (active) inhibits Ced-4 activity signaling molecule (a) No death signalApoptotic Pathways and the Signals That Trigger Them * Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis + Apoptosis can be triggered by: — Anextracellular death-signaling ligand — DNAdamage in the nucleus — Protein misfolding in the endoplasmic reticulum* Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals ¢ Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers rig ier Interdigital tissue = =@ Reception @ Transduction Fas cell-surface Celustered) redeptors coe protein * age cas pase-B aoe Caspase 8 2 ere Thactive- Active Caspase-3 caspase- -3You should now be able to: 1. Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand- gated ion channels 3. List two advantages of a multistep pathway in the transduction stage of cell signaling 4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell 5. Define the term second messenger, briefly describe the role of these molecules in signaling pathways 6. Explain why different types of cells may respond differently to the same signal molecule 7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates