1. Chapter 11
Cell Communication 1

2. Overview: Cellular Messaging
Cell-to-cell communication is essential
Universal mechanisms of cellular regulation
Cells communicate via chemical signals / messengers
Ex. Fight-or-flight response is triggered by a signaling molecule called epinephrine
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3. Ch 11.1: External signals are converted to responses within the cell
Microbes provide a glimpse of the role of cell signaling in the evolution of life
Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes → modified later in eukaryotes
Concentration of signaling molecules allows bacteria to sense local population density
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4. Exchange of mating factors
Figure 11.2
 factor
Receptor 1
Exchange of mating factors a 
a factor
Yeast cell,
mating type a
Yeast cell,
mating type  2
Mating a 
Figure 11.2 Communication between mating yeast cells. 3
New a/ cell
a/ 4

5. Individual rod-shaped cells
Figure 11.3 1
Individual rod-shaped cells 2
Aggregation in progress
0.5 mm 3
Spore-forming structure (fruiting body)
2.5 mm
Figure 11.3 Communication among bacteria.
Fruiting bodies 5

6. Local and Long-Distance Signaling
Animal cells local signaling communicate by:
direct contact
cell-cell recognition
Animal and plant cells: have cell junctions that directly connect the cytoplasm of adjacent cells
Plant: Plasmodesmata
Animal: Gap Junctions
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7. Gap junctions between animal cells Plasmodesmata between plant cells
Figure 11.4
Plasma membranes
Gap junctions between animal cells
Plasmodesmata between plant cells
(a) Cell junctions
Figure 11.4 Communication by direct contact between cells.
(b) Cell-cell recognition 7

8. Local and Long-Distance Signaling (cont)
Local regulators: messenger molecules that travel short distances
Long-distance signaling: plants and animals use chemicals called hormones
The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal
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9. Neurotransmitter diffuses across synapse. Secreting cell
Figure 11.5a
Local signaling
Target cell
Electrical signal along nerve cell triggers release of neurotransmitter.
Neurotransmitter diffuses across synapse.
Secreting cell
Secretory vesicle
Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals.
Local regulator diffuses through extracellular fluid.
Target cell is stimulated.
(a) Paracrine signaling
(b) Synaptic signaling 9

10. Long-distance signaling
Figure 11.5b
Long-distance signaling
Endocrine cell
Blood vessel
Hormone travels in bloodstream.
Target cell specifically binds hormone.
Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals.
(c) Endocrine (hormonal) signaling 10

11. The Three Stages of Cell Signaling:
EXTRACELLULAR FLUID
CYTOPLASM
Plasma membrane 1
Reception 2
Transduction 3
Response
Receptor
Activation of cellular response
Relay molecules in a signal transduction pathway
Signaling molecule
Animation: Overview of Cell Signaling
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12. Ch 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 = initial transduction of the signal
Most signal receptors are plasma membrane proteins
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13. Receptors in the Plasma Membrane
There are three main types of membrane receptors
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors
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14. G protein-coupled receptors (GPCRs)
largest family of cell-surface receptors
works with the help of a G protein
G protein acts as an on/off switch:
If GDP is bound to the G protein, the G protein is inactive
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15. G protein-coupled receptor Plasma membrane Activated receptor
Figure 11.7b
G protein-coupled receptor
Plasma membrane
Activated receptor
Signaling molecule
Inactive enzyme
GTP
GDP
GDP
CYTOPLASM
G protein (inactive)
Enzyme
GTP 1 2
GDP
Activated enzyme
Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
GTP
GDP
P i 3
Cellular response 4 15

16. Receptor tyrosine kinases (RTKs)
membrane receptors that attach phosphates to tyrosines
can trigger multiple signal transduction pathways at once
Abnormal functioning of RTKs is associated with many types of cancers
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17. Signaling molecule (ligand) Ligand-binding site
Figure 11.7c
Signaling molecule (ligand)
Ligand-binding site
 helix in the membrane
Signaling molecule
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
CYTOPLASM
Receptor tyrosine kinase proteins (inactive monomers)
Dimer 1 2
Activated relay proteins
Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
Cellular response 1
Tyr
Tyr P
Tyr
Tyr P
Tyr
Tyr P P
Tyr
Tyr P
Tyr
Tyr
Tyr
Tyr P P P
Cellular response 2
Tyr
Tyr P
Tyr
Tyr P P
Tyr
Tyr P
6 ATP
6 ADP
Activated tyrosine kinase regions (unphosphorylated dimer)
Fully activated receptor tyrosine kinase (phosphorylated dimer)
Inactive relay proteins 3 4 17

18. ligand-gated ion channel
receptor acts as a gate when the receptor changes shape
signal molecule binds as a ligand to the receptor gate → allows specific ions (such as Na+ or Ca2+) through a channel in the receptor
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19. Signaling molecule (ligand)
Figure 11.7d 1 2 3
Gate closed
Ions
Gate open
Gate closed
Signaling molecule (ligand)
Plasma membrane
Ligand-gated ion channel receptor
Cellular response
Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors 19

20. Intracellular Receptors
Intracellular receptor proteins are found in the cytosol or nucleus of target cells
Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors
Ex. steroid and thyroid hormones of animals
An activated hormone-receptor complex can act as a transcription factor, turning on specific genes
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21. Hormone (testosterone) EXTRACELLULAR FLUID
Figure
Hormone (testosterone)
EXTRACELLULAR FLUID
Plasma membrane
Receptor protein
DNA
Figure 11.9 Steroid hormone interacting with an intracellular receptor.
NUCLEUS
CYTOPLASM 21

22. Hormone (testosterone) EXTRACELLULAR FLUID
Figure
Hormone (testosterone)
EXTRACELLULAR FLUID
Plasma membrane
Receptor protein
Hormone- receptor complex
DNA
Figure 11.9 Steroid hormone interacting with an intracellular receptor.
mRNA
NUCLEUS
New protein
CYTOPLASM 22

23. Ch 11.3 Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Usually involves multiple steps:
amplifies a signal: A few molecules can produce a large cellular response
provide more opportunities for coordination and regulation of the cellular response
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24. Signal Transduction Pathways
Receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
like falling dominoes
At each step, the signal is transduced into a different form
usually a shape change in a protein
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25. Protein Phosphorylation and Dephosphorylation
Signal is transmitted by a cascade of protein phosphorylations
Phosphorylation = transfer of phosphates from ATP to protein using protein kinases
Turn ON pathway
Dephosphorylation = remove the phosphates from proteins using protein phosphatases
Turn OFF pathway
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26. Activated relay molecule
Figure 11.10
Signaling molecule
Receptor
Activated relay molecule
Inactive protein kinase 1
Active protein kinase 1
Inactive protein kinase 2
ATP
Phosphorylation cascade
ADP
Active protein kinase 2 P PP
P i
Figure A phosphorylation cascade.
Inactive protein kinase 3
ATP
ADP P
Active protein kinase 3 PP
P i
Inactive protein
ATP
ADP P
Active protein
Cellular response PP
P i 26

27. Activated relay molecule
Figure 11.10a
Activated relay molecule
Inactive protein kinase 1
Active protein kinase 1
Inactive protein kinase 2
ATP
Phosphorylation cascade
ADP
Active protein kinase 2 P PP
P i
Inactive protein kinase 3
ATP
Figure A phosphorylation cascade.
ADP
Active protein kinase 3 P PP
P i
Inactive protein
ATP
ADP P
Active protein PP
P i 27

28. Small Molecules and Ions as Second Messengers
The extracellular signal molecule (ligand) 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
MOST COMMON: Cyclic AMP & calcium ions
participate in pathways initiated by GPCRs and RTKs
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29. Cyclic AMP (cAMP) 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
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30. Adenylyl cyclase Pyrophosphate P P i ATP cAMP Figure 11.11a
Figure Cyclic AMP.
ATP
cAMP 30

31. Phosphodiesterase AMP cAMP H2O H2O Figure 11.11b
Figure Cyclic AMP.
cAMP
AMP 31

32. cAMP formation
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
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33. First messenger (signaling molecule such as epinephrine)
Figure 11.12
First messenger (signaling molecule such as epinephrine)
Adenylyl cyclase
G protein
G protein-coupled receptor
GTP
ATP
Second messenger
cAMP
Figure cAMP as a second messenger in a G protein signaling pathway.
Protein kinase A
Cellular responses 33

34. Calcium Ions and Inositol Triphosphate (IP3)
- Calcium ions (Ca2+) act as a 2nd messenger
cells can regulate its concentration
- Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
Animation: Signal Transduction Pathways
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35. Endoplasmic reticulum (ER)
Figure 11.13
EXTRACELLULAR FLUID
Plasma membrane
Ca2 pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2 pump
Figure The maintenance of calcium ion concentrations in an animal cell.
Endoplasmic reticulum (ER)
Ca2 pump
ATP
Key
High [Ca2 ]
Low [Ca2 ] 35

36. Signaling molecule (first messenger)
Figure
EXTRA- CELLULAR FLUID
Signaling molecule (first messenger)
G protein
DAG
GTP
G protein-coupled receptor
PIP2
Phospholipase C
IP3 (second messenger)
IP3-gated calcium channel
Figure Calcium and IP3 in signaling pathways.
Various proteins activated
Cellular responses
Endoplasmic reticulum (ER)
Ca2
Ca2 (second messenger)
CYTOSOL 36

37. Ch 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
Cell’s response to an extracellular signal called:
“output response”
Ultimately pathway leads to regulation of one or more cellular activities
Response may occur in the cytoplasm or nucleus
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38. Nuclear and Cytoplasmic Responses
Regulate the synthesis of enzymes or other proteins → turn genes on or off in the nucleus
The final activated molecule in the signaling pathway may function as a transcription factor
Regulate the activity of enzymes rather than their synthesis
Affect behavior of a cell
Ex: Changes in cell shape
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39. Inactive transcription factor Active transcription factor
Figure 11.15
Growth factor
Reception
Receptor
Phosphorylation cascade
Transduction
CYTOPLASM
Inactive transcription factor
Active transcription factor
Figure Nuclear responses to a signal: the activation of a specific gene by a growth factor.
Response P
DNA
Gene
NUCLEUS
mRNA 39

40. Glucose 1-phosphate (108 molecules)
Figure 11.16
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)
Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine.
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose 1-phosphate (108 molecules) 40

41. Wild type (with shmoos) Fus3 formin CONCLUSION
Figure 11.17
RESULTS
Wild type (with shmoos)
Fus3
formin
CONCLUSION 1
Mating factor activates receptor.
Mating factor
Shmoo projection forming
G protein-coupled receptor
Formin P
Fus3
Actin subunit
GTP P
GDP 2
Phosphory- lation cascade
G protein binds GTP and becomes activated.
Formin
Formin
Figure Inquiry: How do signals induce directional cell growth during mating in yeast? P 4
Fus3 phos- phorylates formin, activating it.
Microfilament
Fus3
Fus3 P 5
Formin initiates growth of microfilaments that form the shmoo projections. 3
Phosphorylation cascade activates Fus3, which moves
to plasma membrane. 41

42. Fine-Tuning of the Response
There are four aspects of fine-tuning to consider
Amplifying the signal (and thus the response)
Specificity of the response
Overall efficiency of response, enhanced by scaffolding proteins
Termination of the signal
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43. Signal Amplification Enzyme cascades amplify the cell’s response
Number of activated products is greater at each step
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44. The Specificity of Cell Signaling and Coordination of the Response
Different cells = different types / amts of proteins
Allow cells to detect and respond to different signals
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45. Figure 11.18
Signaling molecule
Receptor
Relay molecules
Activation or inhibition
Figure The specificity of cell signaling.
Response 1
Response 2
Response 3
Response 4
Response 5
Cell A. Pathway leads to a single response.
Cell B. Pathway branches, leading to two responses.
Cell C. Cross-talk occurs between two pathways.
Cell D. Different receptor leads to a different response. 45

46. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Scaffolding proteins: lg relay proteins to which other relay proteins attach
can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
may also help activate some of the relay proteins
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47. Three different protein kinases
Figure 11.19
Signaling molecule
Plasma membrane
Receptor
Three different protein kinases
Figure A scaffolding protein.
Scaffolding protein 47

48. 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
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49. Ch 11.5: Apoptosis integrates multiple cell-signaling pathways
Apoptosis is programmed or controlled cell suicide
prevents enzymes from leaking out of a dying cell and damaging neighboring cells
Cell chopped up, packaged into vesicles, digested by scavenger cells
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50. 2 m Figure 11.20 Figure 11.20 Apoptosis of a human white blood cell.50

51. Apoptosis in the Soil Worm Caenorhabditis elegans
Important in shaping an organism during embryonic development
Results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis
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52. Ced-9 protein (active) inhibits Ced-4 activity
Figure 11.21
Ced-9 protein (active) inhibits Ced-4 activity
Ced-9 (inactive)
Cell forms blebs
Death- signaling molecule
Mitochondrion
Active Ced-4
Active Ced-3
Other proteases
Ced-4
Ced-3
Nucleases
Receptor for death- signaling molecule
Activation cascade
Figure Molecular basis of apoptosis in C. elegans.
Inactive proteins
(a) No death signal
(b) Death signal 52

53. 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
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54. Apoptosis Connection To Us
Essential for the development and maintenance of all animals
May be involved in some diseases
Ex: Parkinson’s and Alzheimer’s
Interference with apoptosis may contribute to some cancers (P53 gene)
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55. Cells undergoing apoptosis
Figure 11.22
Cells undergoing apoptosis
Space between digits
1 mm
Interdigital tissue
Figure Effect of apoptosis during paw development in the mouse. 55