1. Cell Communication

2. Cell Communication: 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
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3. Evolution of Cell Signaling
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
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4. Evolution of Cell Signaling
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
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5. 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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6. Gap junctions between animal cells Plasmodesmata between plant cells
Fig. 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. Local vs. Long Distance Signaling
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
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8. (a) Paracrine signaling (b) Synaptic signaling
Fig. 11-5ab
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 communication in animals
Local regulator
diffuses through
extracellular fluid
Target cell
is stimulated
(a) Paracrine signaling
(b) Synaptic signaling

9. Long-distance signaling
Fig. 11-5c
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Figure 11.5 Local and long-distance cell communication in animals
Target
cell
(c) Hormonal signaling

10. The Three Stages of Cell Signaling:
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
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11. Plasma membrane 1 Reception Transduction Response Receptor Activation
Fig
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1
Reception 2
Transduction 3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Figure 11.6 Overview of cell signaling
Signaling
molecule

12. Most signal receptors are plasma membrane proteins
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
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13. Membrane Receptors There are three main types of membrane receptors:
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors
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14. 1. G Protein-Coupled Receptor
Membrane receptor
Works with the help of a G protein, a protein that binds the energy rich molecule GTP.
The 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. Signaling-molecule binding site
Fig. 11-7a
Signaling-molecule binding site
Figure 11.7 Membrane receptors—G protein-coupled receptors, part 1
Segment that
interacts with
G proteins
G protein-coupled receptor

16. Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2
Fig. 11-7b
Plasma
membrane
G protein-coupled
receptor
Inactive
enzyme
Activated
receptor
Signaling molecule
GDP
G protein
(inactive)
Enzyme
GDP
GTP
CYTOPLASM 1 2
Activated
enzyme
Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2
GTP
GDP P i
Cellular response 3 4

17. 2. Receptor Tyrosine Kinases
membrane receptors
Have enzymatic activity
attach phosphates to tyrosines
Can trigger multiple signal transduction pathways at once, therefore can help cell regulate and co-ordinate cell growth and reproduction
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18. Fully activated receptor tyrosine kinase
Fig. 11-7c
Signaling
molecule (ligand)
Ligand-binding site
Signaling
molecule
 Helix
Tyr
Tyr
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
Dimer
CYTOPLASM 1 2
Activated relay
proteins
Figure 11.7 Membrane receptors—receptor tyrosine kinases
Cellular
response 1
Tyr
Tyr P
Tyr
Tyr P
Tyr
Tyr P P
Tyr
Tyr P
Tyr
Tyr P
Tyr
Tyr P P
Cellular
response 2
Tyr
Tyr P
Tyr
Tyr P
Tyr P
Tyr P 6
ATP
6 ADP
Activated tyrosine
kinase regions
Fully activated receptor
tyrosine kinase
Inactive
relay proteins 3 4

19. 3. Ligand-gated ion channel
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
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20. 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane
Fig. 11-7d 1
Signaling
molecule
(ligand)
Gate
closed
Ions
Plasma
membrane
Ligand-gated
ion channel receptor 2
Gate open
Cellular
response
Figure 11.7 Membrane receptors—ion channel receptors 3
Gate closed

21. Intracellular Receptors
Some receptor proteins are intracellular, 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
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22. Hormone (testosterone) Plasma membrane Receptor protein Hormone-
Fig
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
Figure 11.8 Steroid hormone interacting with an intracellular receptor
mRNA
NUCLEUS
New protein
CYTOPLASM

23. Usually involves multiple steps
Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Usually involves multiple steps
Can amplify 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
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.
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25. Protein Phosphorylation and Dephosphorylation
In many pathways, the signal is transmitted by a cascade of protein phosphorylations, carried out by protein kinases, which transfer phosphates from ATP to protein.
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
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26. Phosphorylation cascade
Fig. 11-9
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 11.9 A phosphorylation cascade
Inactive
protein kinase 3
ATP
ADP
Active
protein
kinase 3 P PP P i
Inactive
protein
ATP
ADP P
Active
protein
Cellular
response PP P i

27. 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
Cyclic AMP and calcium ions are common second messengers
Adenyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
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28. Fig. 11-10 Figure 11.10 Cyclic AMP Adenylyl cyclase Phosphodiesterase
Pyrophosphate P P i
ATP
cAMP
AMP
Figure Cyclic AMP

29. First messenger Adenylyl cyclase G protein GTP G protein-coupled
Fig
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
Second
messenger
cAMP
Figure cAMP as second messenger in a G-protein-signaling pathway
Protein
kinase A
Cellular responses

30. Calcium Ions
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration
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31. EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion
Fig
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+ pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
Figure The maintenance of calcium ion concentrations in an animal cell
Ca2+
pump
ATP
Key
High [Ca2+]
Low [Ca2+]

32. The final activated molecule may function as a transcription factor
Response: Cell signaling leads to regulation of transcription or cytoplasmic activities
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
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33. Growth factor Reception Receptor Phosphorylation cascade Transduction
Fig
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

34. 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
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35. Fig. 11-17 Figure 11.17 The specificity of cell signaling Signaling
molecule
Receptor
Relay
molecules
Response 1
Response 2
Response 3
Cell A. Pathway leads
to a single response.
Cell B. Pathway branches,
leading to two responses.
Figure The specificity of cell signaling
Activation
or inhibition
Response 4
Response 5
Cell C. Cross-talk occurs
between two pathways.
Cell D. Different receptor
leads to a different response.

36. 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
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37. Signaling Plasma molecule membrane Receptor Three different protein
Fig
Signaling
molecule
Plasma
membrane
Receptor
Three
different
protein
kinases
Figure A scaffolding protein
Scaffolding
protein

38. Termination of the Signal
When signal molecules leave the receptor, the receptor reverts to its inactive state
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39. Apoptosis Programmed or controlled cell death
Integrates multiple cell-signaling pathways
Cell is chopped and packaged into vesicles that are digested by scavenger cells
Prevents enzymes from leaking out of a dying cell and damaging neighboring cells
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40. 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
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41. Signals That Trigger Apoptosis
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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