Chapter 11
Cell Communication
PowerPoint Lecture Presentations for
Biology
Eighth Edition Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Evolution of Cell Signaling A signal transduction pathway is a series of steps by which a signal on a cells surface is converted into a specific cellular response Signal transduction pathways convert signals on a cells surface into cellular responses
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-2
Receptor
factor
Exchange of mating factors
Yeast cell, mating type a
a factor
Yeast cell, mating type
Mating
New a/ cell
a/
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-3
1 Individual rodshaped cells
2 Aggregation in process
0.5 mm
3 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
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Fig. 11-4
Plasma membranes
Gap junctions between animal cells (a) Cell junctions
Plasmodesmata between plant cells
(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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-5
Local signaling Electrical signal along nerve cell triggers release of neurotransmitter
Long-distance signaling Endocrine cell Blood vessel
Target cell
Secreting cell
Secretory vesicle
Neurotransmitter diffuses across synapse
Hormone travels in bloodstream to target cells
Local regulator diffuses through extracellular fluid (a) Paracrine signaling
Target cell is stimulated (b) Synaptic signaling
Target cell
(c) Hormonal signaling
Fig. 11-5ab
Local signaling
Target cell
Electrical signal along nerve cell triggers release of neurotransmitter
Secreting cell
Secretory vesicle
Neurotransmitter diffuses across synapse
Local regulator diffuses through extracellular fluid (a) Paracrine signaling
Target cell is stimulated (b) Synaptic signaling
Fig. 11-5c
Long-distance signaling Endocrine cell Blood vessel
Hormone travels in bloodstream to target cells
Target cell
(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
Animation: Overview of Cell Signaling
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-6-1
EXTRACELLULAR FLUID
CYTOPLASM
Plasma membrane
1 Reception Receptor
Signaling molecule
Fig. 11-6-2
EXTRACELLULAR FLUID
CYTOPLASM
Plasma membrane
2 Transduction
1 Reception Receptor
Relay molecules in a signal transduction pathway
Signaling molecule
Fig. 11-6-3
EXTRACELLULAR FLUID
CYTOPLASM
Plasma membrane
2 Transduction 3 Response
1 Reception Receptor
Activation of cellular response
Relay molecules in a signal transduction pathway
Signaling molecule
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 A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Ion channel receptors
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
A G 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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7a
Signaling-molecule binding site
Segment that interacts with G proteins
G protein-coupled receptor
Fig. 11-7b
G protein-coupled receptor
Plasma membrane
Activated receptor
Signaling molecule
Inactive enzyme
GDP CYTOPLASM 1 G protein (inactive) Enzyme GDP GTP
Activated enzyme
GTP
GDP
Pi
Cellular response 3 4
Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
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Fig. 11-7c
Signaling molecule (ligand) Helix
Ligand-binding site Signaling molecule
Tyrosines
Tyr Tyr Tyr
Tyr Tyr Tyr
Tyr Tyr Tyr
Tyr Tyr Tyr
Tyr Tyr Tyr
Tyr Tyr Tyr
CYTOPLASM
1
Receptor tyrosine kinase proteins
2
Dimer
Activated relay proteins
Tyr
Tyr Tyr Tyr
Tyr
Tyr
P Tyr P Tyr
Tyr Tyr
6 ATP
6 ADP
Tyr
P P Tyr P
P Tyr P Tyr P Tyr
Tyr Tyr Tyr
P P P
Cellular response 1 Cellular response 2
Activated tyrosine kinase regions
Fully activated receptor tyrosine kinase Inactive relay proteins
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-7d
1 Signaling molecule (ligand)
Gate closed
Ions
Ligand-gated ion channel receptor 2 Gate open
Plasma membrane
Cellular response
Gate closed
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-8-1
Hormone (testosterone)
EXTRACELLULAR FLUID
Receptor protein
Plasma membrane
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-2
Hormone (testosterone)
EXTRACELLULAR FLUID
Receptor protein
Plasma membrane
Hormonereceptor complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-3
Hormone (testosterone)
EXTRACELLULAR FLUID
Receptor protein
Plasma membrane
Hormonereceptor complex
DNA
NUCLEUS
CYTOPLASM
Fig. 11-8-4
Hormone (testosterone)
EXTRACELLULAR FLUID
Receptor protein
Plasma membrane Hormonereceptor complex
DNA mRNA
NUCLEUS
CYTOPLASM
Fig. 11-8-5
Hormone (testosterone)
EXTRACELLULAR FLUID
Receptor protein
Plasma membrane
Hormonereceptor complex
DNA mRNA
NUCLEUS
New protein
CYTOPLASM
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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 At each step, the signal is transduced into a different form, usually a shape change in a protein
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-9
Signaling molecule
Receptor Activated relay molecule
Inactive protein kinase 1
Active protein kinase 1
Inactive protein kinase 2
Pi ATP ADP
PP
Active protein kinase 2
ATP ADP
Inactive protein kinase 3
Pi
PP
Inactive protein
Active protein kinase 3
ATP ADP
Pi
PP
Active protein
Cellular response
Small Molecules and Ions as Second Messengers The extracellular signal molecule that binds to the receptor is a pathways 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 messengers
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-10
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate P ATP Pi
cAMP
AMP
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-11
First messenger
G protein
Adenylyl cyclase
G protein-coupled receptor
GTP ATP cAMP
Second messenger Protein kinase A
Cellular responses
Calcium Ions and Inositol Triphosphate (IP3) Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-12
EXTRACELLULAR FLUID Ca2+ pump ATP Mitochondrion
Plasma membrane
Nucleus
CYTOSOL
Ca2+ pump Endoplasmic reticulum (ER) ATP Ca2+ pump
Key High [Ca2+] Low [Ca2+]
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
Animation: Signal Transduction Pathways
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-13-1
EXTRACELLULAR FLUID
Signaling molecule (first messenger)
G protein DAG
GTP
G protein-coupled receptor
Phospholipase C
PIP2 IP3 (second messenger)
IP3-gated calcium channel
Endoplasmic reticulum (ER)
Ca2+
CYTOSOL
Fig. 11-13-2
EXTRACELLULAR FLUID
Signaling molecule (first messenger) G protein DAG
GTP
G protein-coupled receptor
Phospholipase C
PIP2 IP3 (second messenger)
IP3-gated calcium channel
Endoplasmic reticulum (ER)
Ca2+ Ca2+ (second messenger )
CYTOSOL
Fig. 11-13-3
EXTRACELLULAR FLUID
Signaling molecule (first messenger) G protein DAG
GTP
G protein-coupled receptor
Phospholipase C
PIP2 IP3 (second messenger)
IP3-gated calcium channel
Endoplasmic reticulum (ER)
Ca2+ Ca2+ (second messenger )
Various proteins activated
Cellular responses
CYTOSOL
Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities The cells response to an extracellular signal is sometimes called the output response
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-14
Growth factor Receptor
Reception
Phosphorylatio n cascade
Transduction
CYTOPLASM
Inactive transcription factor
Active transcription factor
P
Response
DNA Gene NUCLEUS mRNA
Other pathways regulate the activity of enzymes
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-15 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 (104)
Inactive phosphorylase kinase Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response Glycogen Glucose-1-phosphate (108 molecules)
Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-16
RESULTS
Wild-type (shmoos)
Fus3
formin
CONCLUSION
1
Mating factor G protein-coupled receptor
Shmoo projection forming Formin P Fus3 Actin subunit
GDP
2
GTP Phosphorylation cascade
Formin
P
4
Formin
Fus3 P
Fus3
Microfilament
5
Fig. 11-16a
RESULTS
Wild-type (shmoos)
Fus3
formin
Fig. 11-16b
CONCLUSION
1
Mating factor G protein-coupled receptor
Shmoo projection forming
Formin P Fus3 Actin subunit Formin P
4
GDP
2
GTP Phosphorylation cascade
P Formin
Fus3 P
Fus3
Microfilament
5
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Signal Amplification Enzyme cascades amplify the cells response At each step, the number of activated products is much greater than in the preceding step
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-17
Signaling molecule
Receptor
Relay molecules
Response 1 Cell A. Pathway leads to a single response.
Response 2
Response 3
Cell B. Pathway branches, leading to two responses.
Activation or inhibition
Response 4
Response 5
Cell C. Cross-talk occurs between two pathways.
Cell D. Different receptor leads to a different response.
Fig. 11-17a
Signaling molecule
Receptor
Relay molecules
Response 1 Cell A. Pathway leads to a single response.
Response 2
Response 3
Cell B. Pathway branches, leading to two responses.
Fig. 11-17b
Activation or inhibition
Response 4 Cell C. Cross-talk occurs between two pathways.
Response 5 Cell D. Different receptor 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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-18
Signaling molecule
Plasma membrane
Receptor
Three different protein kinases Scaffolding protein
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-19
2 m
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-20
Ced-9 protein (active) inhibits Ced-4 activity
Mitochondrion
Receptor for deathsignaling molecule
Ced-4 Ced-3 Inactive proteins
(a) No death signal
Ced-9 (inactive)
Cell forms blebs
Deathsignaling molecule
Active Active Ced-4 Ced-3
Other proteases Nucleases
Activation cascade
(b) Death signal
Fig. 11-20a
Ced-9 protein (active) inhibits Ced-4 activity
Mitochondrion
Receptor for deathsignaling molecule
Ced-4 Ced-3 Inactive proteins
(a) No death signal
Fig. 11-20b
Ced-9 (inactive)
Cell forms blebs
Deathsignaling molecule
Active Active Ced-4 Ced-3
Other proteases Nucleases
Activation cascade
(b) 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:
An extracellular death-signaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic reticulum
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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, Parkinsons and Alzheimers); interference with apoptosis may contribute to some cancers
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Fig. 11-21
Interdigital tissue
1 mm
Fig. 11-UN1
Reception
Transduction
3 Response
Receptor Activation of cellular response
Relay molecules
Signaling molecule
Fig. 11-UN2
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 ligandgated 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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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
Copyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
