Chapter 11 Cell Communication 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 oweroint Lecture resentations for Biology Eighth Edition Neil Campbell and Jane Reece For example, the dilation of blood vessels is controlled by multiple s Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Fig. 11-1 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 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 Fig. 11-2 1 Exchange of mating factors a α a factor Yeast cell, Yeast cell, mating type a mating type α Signal transduction pathways convert signals on a cell s surface into cellular responses α factor 2 Mating 3 New a/α cell a α a/α
Fig. 11-3 athway similarities suggest that ancestral signaling s evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling s allows bacteria to detect population density 3 1 Individual rodshaped cells Spore-forming structure (fruiting body) 0.5 mm 2 Aggregation in process Fruiting bodies Local and Long-Distance Fig. 11-4 lasma s 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 Gap junctions between animal cells (a) Cell junctions lasmodesmata between plant cells (b) Cell-cell recognition Fig. 11-5 In many other cases, animal cells communicate using local regulators, messenger s that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones Secreting cell Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Local signaling Target cell is stimulated Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Long-distance signaling Endocrine cell Target cell Blood vessel Hormone travels in bloodstream to target cells (a) aracrine signaling (b) Synaptic signaling (c) Hormonal signaling
Fig. 11-5ab Fig. 11-5c Long-distance signaling Target cell Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Endocrine cell Blood vessel Secreting cell Secretory vesicle Neurotransmitter diffuses across synapse Hormone travels in bloodstream to target cells Local regulator diffuses through extracellular fluid Target cell is stimulated Target cell (a) aracrine signaling (b) Synaptic signaling (c) Hormonal signaling The Three Stages of Cell : A review Fig. 11-6-1 Earl W. Sutherland discovered how the hormone epinephrine acts on cells lasma CYTOLASM Sutherland suggested that cells receiving signals went through three processes: Reception Transduction Response 1 Reception Animation: Overview of Cell Fig. 11-6-2 Fig. 11-6-3 lasma CYTOLASM lasma CYTOLASM 1 Reception 2 Transduction Relay s in a signal transduction pathway 1 Reception 2 Transduction 3 Response Relay s in a signal transduction pathway Activation of cellular response
Concept 11.2: Reception: A signal binds to a, causing it to change shape The binding between a signal (ligand) and is highly specific A shape change in a is often the initial transduction of the signal Most signal s are plasma s s in the lasma Membrane Most water-soluble signal s bind to specific sites on s in the plasma There are three main types of s: G -coupled s tyrosine kinases Ion channel s Fig. 11-7a - binding site A G -coupled is a plasma that works with the help of a G The G acts as an on/off switch: If GD is bound to the G, the G is inactive Segment that interacts with G s G -coupled Fig. 11-7b G -coupled CYTOLASM GD lasma G (inactive) Enzyme 1 2 Activated GD GT Inactive enzyme tyrosine kinases are s that attach phosphates to tyrosines A tyrosine kinase can trigger multiple signal transduction pathways at once Activated enzyme GT GD i Cellular response 3 4
Fig. 11-7c (ligand) α Helix osines CYTOLASM Ligand-binding site tyrosine kinase s 1 2 Activated relay s Dimer A ligand-gated ion channel acts as a gate when the changes shape When a signal binds as a ligand to the, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the 6 AT 6 AD Cellular response 1 Cellular response 2 Activated tyrosine kinase regions Fully activated tyrosine kinase Inactive relay s 3 4 Fig. 11-7d 1 Intracellular s (ligand) Gate closed Ions 2 3 Ligand-gated ion channel Gate open Gate closed lasma Cellular response Some s are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the and activate s Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone- complex can act as a transcription factor, turning on specific genes Fig. 11-8-1 Hormone (testosterone) Fig. 11-8-2 Hormone (testosterone) lasma lasma Hormone complex DNA DNA NUCLEUS NUCLEUS CYTOLASM CYTOLASM
Fig. 11-8-3 Hormone (testosterone) Fig. 11-8-4 Hormone (testosterone) lasma Hormone complex lasma Hormone complex DNA DNA mrna NUCLEUS NUCLEUS CYTOLASM CYTOLASM Fig. 11-8-5 Hormone (testosterone) lasma Hormone complex Concept 11.3: Transduction: Cascades of molecular interactions relay signals from s to target s in the cell Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few s can produce a large cellular response mrna NUCLEUS DNA New Multistep pathways provide more opportunities for coordination and regulation of the cellular response CYTOLASM Signal Transduction athways rotein hosphorylation and Dephosphorylation The s that relay a signal from to response are mostly s Like falling dominoes, the activates another, which activates another, and so on, until the producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a In many pathways, the signal is transmitted by a cascade of phosphorylations rotein kinases transfer phosphates from AT to, a process called phosphorylation
Fig. 11-9 rotein phosphatases remove the phosphates from s, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Activated relay Inactive kinase 1 kinase 1 Inactive kinase 2 i AT AD Inactive kinase 3 i AT kinase 2 AD Inactive i AT hosphorylation cascade kinase 3 AD Cellular response Small Molecules and Ions as Second Messengers Cyclic AM The extracellular signal that binds to the is a pathway s first messenger Second messengers are small, non, water-soluble s or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by G -coupled s and tyrosine kinases Cyclic AM and calcium ions are common second messengers Cyclic AM (cam) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma, converts AT to cam in response to an extracellular signal Fig. 11-10 Many signal s trigger formation of cam AT Adenylyl cyclase yrophosphate i cam hosphodiesterase AM Other components of cam pathways are G s, G -coupled s, and kinases cam usually activates kinase A, which phosphorylates various other s Further regulation of cell metabolism is provided by G- systems that inhibit adenylyl cyclase
Fig. 11-11 First messenger Calcium Ions and Inositol Triphosphate (I 3 ) G Adenylyl cyclase Calcium ions (Ca 2+ ) act as a second messenger in many pathways G -coupled GT Calcium is an important second messenger because cells can regulate its concentration AT cam Second messenger rotein kinase A Cellular responses Fig. 11-12 lasma CYTOSOL AT AT Mitochondrion Nucleus Ca 2+ pump Ca 2+ pump Ca 2+ pump Endoplasmic reticulum (ER) 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 Key High [Ca 2+ ] Low [Ca 2+ ] Animation: Signal Transduction athways Fig. 11-13-1 Fig. 11-13-2 EXTRA- CELLULAR (first messenger) EXTRA- CELLULAR (first messenger) G G DAG DAG G -coupled GT hospholipase C I 2 G -coupled GT hospholipase C I 2 I 3 (second messenger) I 3 (second messenger) I 3 -gated calcium channel I 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ Endoplasmic reticulum (ER) Ca 2+ CYTOSOL CYTOSOL Ca 2+ (second messenger)
Fig. 11-13-3 EXTRA- CELLULAR (first messenger) G -coupled G GT hospholipase C I 2 DAG 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 I 3 (second messenger) I 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ Various s activated Cellular responses CYTOSOL Ca 2+ (second messenger) Nuclear and Cytoplasmic Responses Fig. 11-14 Growth factor Reception 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 s, usually by turning genes on or off in the nucleus The final activated may function as a transcription factor CYTOLASM DNA Inactive transcription factor hosphorylation cascade transcription factor Transduction Response Gene NUCLEUS mrna Fig. 11-15 Reception Binding of epinephrine to G -coupled (1 ) Other pathways regulate the activity of enzymes Transduction Inactive G G (10 2 s) Inactive adenylyl cyclase adenylyl cyclase (10 2 ) AT Cyclic AM (10 4 ) Inactive kinase A kinase A (10 4 ) Inactive phosphorylase kinase phosphorylase kinase (10 5 ) Inactive glycogen phosphorylase glycogen phosphorylase (10 6 ) Response Glycogen Glucose-1-phosphate (10 8 s)
Fig. 11-16 RESULTS pathways can also affect the physical characteristics of a cell, for example, cell shape Wild-type (shmoos) Fus3 formin CONCLUSION 1 Mating factor G -coupled Shmoo projection forming Formin GD 2 GT hosphorylation cascade Fus3 Formin Formin Actin subunit 4 Fus3 Fus3 Microfilament 3 5 Fig. 11-16a Fig. 11-16b CONCLUSION RESULTS 1 Mating factor G -coupled Shmoo projection forming Formin GD 2 GT hosphorylation cascade Fus3 Formin Formin Actin subunit 4 Wild-type (shmoos) Fus3 formin Fus3 Fus3 3 Microfilament 5 Fine-Tuning of the Response Signal Amplification Multistep pathways have two important benefits: Amplifying the signal (and thus the response) Contributing to the specificity of the response Enzyme cascades amplify the cell s response At each step, the number of activated products is much greater than in the preceding step
The Specificity of Cell and Coordination of the Response Fig. 11-17 Different kinds of cells have different collections of s Relay s These different s allow cells to detect and respond to different signals Response 1 Cell A. athway leads to a single response. Response 2 Response 3 Cell B. athway branches, leading to two responses. Even the same signal can have different effects in cells with different s and pathways athway branching and cross-talk further help the cell coordinate incoming signals Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different leads to a different response. Fig. 11-17a Fig. 11-17b Relay s Activation or inhibition Response 1 Response 2 Response 3 Response 4 Response 5 Cell A. athway leads to a single response. Cell B. athway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different leads to a different response. Efficiency: Scaffolding roteins and Complexes Fig. 11-18 Scaffolding s are large relay s to which other relay s are attached Scaffolding s can increase the signal transduction efficiency by grouping together different s involved in the same pathway Scaffolding lasma Three different kinases
Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling When signal s leave the, the reverts to its inactive state Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide A cell 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 Fig. 11-19 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 s that accelerate apoptosis override those that put the brakes on apoptosis 2 µm Fig. 11-20 Fig. 11-20a Ced-9 (active) inhibits Ced-4 activity Mitochondrion Ced-9 (active) inhibits Ced-4 activity for deathsignaling Ced-4 Ced-3 Inactive s Mitochondrion (a) No death signal Ced-9 (inactive) Cell forms blebs Deathsignaling Ced-4 Ced-3 Activation cascade Other proteases Nucleases for deathsignaling Ced-4 Ced-3 Inactive s (b) Death signal (a) No death signal
Fig. 11-20b Deathsignaling Ced-9 (inactive) Ced-4 Ced-3 Activation cascade Other proteases Nucleases Cell forms blebs Apoptotic athways and the Signals That Trigger Them Caspases are the main proteases (enzymes that cut up s) that carry out apoptosis Apoptosis can be triggered by: An extracellular death-signaling ligand DNA damage in the nucleus rotein misfolding in the endoplasmic reticulum (b) Death signal Fig. 11-21 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, arkinson s and Alzheimer s); interference with apoptosis may contribute to some cancers Interdigital tissue 1 mm Fig. 11-UN1 Fig. 11-UN2 1 Reception 2 Transduction 3 Response Relay s Activation of cellular response
You should now be able to: 1. Describe the nature of a ligand- interaction and state how such interactions initiate a signal-transduction system 2. Compare and contrast G -coupled s, tyrosine kinase s, and ligandgated ion channels 3. List two advantages of a multistep pathway in the transduction stage of cell signaling 4. Explain how an original signal 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 s in signaling pathways 6. Explain why different types of cells may respond differently to the same signal 7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates