1. Cellular Communication
References: Chapter 11 Campbell Biology 7th edition
Chapter 5, Section 5.6 “Biology In Focus” text
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3. Essential knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response.
a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic.
To foster student understanding of this concept, instructors can choose an illustrative example such as:
• Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera
• Effects of neurotoxins, poisons, pesticides
• Drugs (Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs)
✘✘ Specific mechanisms of these diseases and action of drugs are beyond the scope of the course and the AP Exam.

4. Overview: The Cellular Internet
Cell-to-cell communication is absolutely essential for multicellular organisms
Many living organisms contain billions of cells that carry out diverse functions.
In order for the cells to cooperate, cells need to be able to communicate with each other. Most cell signals are chemical in nature.
Many of the genes that cells are capable of synthesizing are thought to be involved in cellular signaling (a.k.a. “signal transduction”).

5. Signal transduction pathways
Concept 11.1: External signals are converted into responses within the cell
Biologists have discovered some universal mechanisms of cellular regulation
Signal transduction pathways
Convert signals on a cell’s surface into cellular responses
Similar in microbes and mammals, suggesting an early evolutionary origin
Figure 11.1

6. Evolution of Cell Signaling
Yeast cells
Identify their mates by cell signaling
 factor
Receptor
Exchange of mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type. 1
Mating. Binding
of the factors to
    receptors
induces changes
     in the cells that
    lead to their
    fusion.
New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and a cells. 2 3
Yeast cell,
mating type a
mating type  
a/ a
Figure 11.2

7. Local and Long-Distance Signaling
Cells in a multicellular organism
Communicate via chemical messengers, called “ligands”
Ligands are signal-triggering molecules, binding to a site on a target protein.
Very specific fit (shape) required to “dock” with receptor

8. Chemical Signaling Between Cells
Three general categories of chemical signaling:
Cytoplasmic connections between cells
Cell-to-cell contact-mediated signaling
Free diffusion between cells
Distant cells (hormones)
Adjacent cells (local signaling)

9. Chemical Signaling Between Cells

10. Cell Junctions: cytoplasmic connections
Animal and plant cells
Have cell junctions that directly connect the cytoplasm of adjacent cells
Plasma membranes
Plasmodesmata
between plant cells
Gap junctions
between animal cells
Figure 11.3
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.

11. In local signaling, animal cells
Direct Contact
In local signaling, animal cells
May communicate via direct contact
Figure 11.3
(b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.

12. Local Signaling
Paracrine signaling is a form of cell signaling in which the target cell is near ("para" = near) the signal-releasing cell.
Mode of action: Most of these molecules degrade very quickly, limiting the scope of their effectiveness to the immediate surroundings. Paracrine molecules must not be allowed to diffuse too far.
Examples: Growth factor and clotting factors are paracrine signaling agents. The local action of growth factor signaling plays an especially important role in the development of tissues.

13. Local Signaling b. Paracrine Signaling Secretory cell Adjacent
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Paracrine Signaling
Secretory cell
Adjacent
target cells b.

14. Local Diffusion e.g., Interferon release by viral-infected cells
e.g., Histamine released from damaged cells in inflammation

15. Neurotransmitters
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neurotransmitters are secreted by neurons to stimulate an adjoining cell
Synaptic Signaling
For example, a neuron might secrete acetylcholine to stimulate the movement of a muscle cell.
Nerve cell
Neurotransmitter
Synaptic gap
Target cell .

16. Note both absence of and lack-of-dependence on Systemic Circulation
Local Diffusion
Note both absence of and lack-of-dependence on Systemic Circulation

17. Hormones: long-distance signaling
Hormones are used for communication with distant target cells. For example, cells can secret a chemical and rely on the blood system to deliver the signal to a distant cell.
Hormone travels
in bloodstream
to target cells
(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood Hormones may reach virtually all body cells.
Long-distance signaling
Blood
vessel
Target
cell
Endocrine cell

18. Long-Distance Diffusion
Note how specificity is determined by receptor protein on target cells
Note dependence on Systemic Circulation (blood/lymph)
Long-Distance Diffusion

19. Ligand – Receptor Binding
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External environment
Cytoplasm
Signal
transduction
pathway
Cellular
response
Extracellular Membrane receptor
Signal
transduction
pathway
Cellular
response
Hydrophilic
ligand
Intracellular receptor
Hydrophobic
ligand
Plasma membrane

20. Intracellular reception
e.g., steroid hormones
Intracellular receptors are cytoplasmic or nuclear proteins
Signal molecules that are small or hydrophobic and can readily cross the plasma membrane use these receptors
e.g., nitric oxide

21. Step 1: Reception:
A signal molecule binds to a receptor protein, causing it to change shape
The binding between signal molecule (ligand) and receptor is highly specific (“lock-and-key”)
A conformational change in a receptor is often the initial transduction of the signal

22. Intracellular Reception

23. Example: testosterone
Binds to intracellular receptors
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasma
membrane
Hormone-
receptor
complex
New protein
Figure 11.6 1
The steroid
hormone testosterone
passes through the
plasma membrane.
Testosterone binds
to a receptor protein
in the cytoplasm,
activating it. 2
The hormone-
receptor complex
enters the nucleus
and binds to specific
genes. 3
The bound protein
stimulates the
transcription of
the gene into mRNA. 4
The mRNA is
translated into a
specific protein. 5

24. Signal-Transduction Emphasis
This chapter’s emphasis is on signals that are released from one cell and allowed to freely diffuse to a second (or more) recipient cell(s)
These communications are deliberately initiated, received, and interpreted in order to increase the physiological coordination of the cells in multicellular organisms
We will consider in particular those events that follow the reception of chemical signals
We will not dwell on the purpose of the signal
We also will not dwell on why and how a given cell released a given signal

25. Extracellular reception
e.g., insulin
e.g., epinephrine

26. Three Stages of Signal Transduction
Reception of extracellular signal by cell
Transduction of signal from outside of cell to inside of cell—often multi-stepped
Cellular Response
Response is initiated and/or occurs entirely within receiving cell

27. Three Stages 1. Reception 2a. Transduction 2b. Transduction
3. Response

28. Three Stages of Signal Transduction
Activity: “play with clay”

29. Transduction: signal boosting
1. Reception
2a. Transduction
2b. Transduction
Transduction: signal boosting
2c. Transduction
2d. Transduction
3. Response
(Responses usually involve increasing or decreasing some Protein’s Function)

30. Note that more than one response can result from the reception of a single ligand
Various Responses

31. Step 3: Response (various possibilities)

32. Receptors in the Plasma Membrane
There are three main types of membrane receptors
G-protein-linked
Tyrosine kinases
Ion channel

33. Examples of Surface Receptors

34. G Protein-Linked Receptors
McGraw Hill animation Action of Epinephrine on a Liver Cell

35. 036 Evolutionary Significance of Cell Communication (7:01 )

36. 037 Cell Communication (10:34)

37. Signal Transduction Pathways (9:24)

38. 039 Effects of Changes in Pathways (5:43)

39. G-protein-linked receptors
G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins
G-protein-linked
Receptor
Plasma Membrane
Enzyme
G-protein (inactive)
CYTOPLASM
Cellular response
Activated
enzyme
Activated Receptor
Signal molecule
Inctivate
Segment that
interacts with
G proteins
GDP
GTP
P i
Signal-binding site
Figure 11.7

40. G Protein-Linked Receptors
the more ligand binding, the greater the cellular response
G Protein-Linked Receptors
note how activation is reversible

41. G Protein-Linked Receptors
the more ligand binding, the more K+ in cytoplasm
G Protein-Linked Receptors

42. Tyrosine Kinase Receptors
Note steps involved:
Ligand Reception
Receptor Dimerization
Catalysis (Phosphorylization)
Subsequent Protein Activation
Further Transduction
Response

43. Tyrosine Kinase Receptors

44. Ion-Channel Receptors

45. Transduction
Cascades of molecular interactions relay signals from receptors to target molecules in the cell
Multistep pathways
Can amplify a signal
Provide more opportunities for coordination and regulation

46. Each protein in a signaling pathway
Signal Amplification
Each protein in a signaling pathway
Amplifies the signal by activating multiple copies of the next component in the pathway

47. Signal Amplification (Cascade)
Note how, via catalysis, one ligand molecule binding gives rise to many new intracellullar molecules
Signal Amplification (Cascade)

48. Protein Phosphorylation and Dephosphorylation
Many signal pathways
Include phosphorylation cascades
In this process
A series of protein kinases add a phosphate to the next one in line, activating it
Phosphatase enzymes then remove the phosphates

49. A phosphorylation cascade
Signal molecule
Active
protein
kinase 1 2 3
Inactive
protein kinase
Cellular
response
Receptor P
ATP
ADP PP
Activated relay
molecule i
Phosphorylation cascade P 
A relay molecule
activates protein kinase 1. 1 2
Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active protein kinase 2
then catalyzes the phos-
phorylation (and activation) of
protein kinase 3. 3
Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse. 5
Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal. 4
Figure 11.8

50. Small Molecules and Ions as Second Messengers
Are small, nonprotein, water-soluble molecules or ions
Examples of second messengers such as inositol triphosphate and diacylglycerol
Can trigger an increase in calcium in the cytosol
Calcium ions and Inositol Triphosphate (IP3)
Calcium, when released into the cytosol of a cell acts as a second messenger in many different pathways

51. Second Messengers

52. Calcium is an important second messenger
Because cells are able to regulate its concentration in the cytosol
EXTRACELLULAR
FLUID
Plasma
membrane
ATP
CYTOSOL
Ca2+ pump
Endoplasmic
reticulum (ER)
Nucleus
Mitochondrion
Key
High [Ca2+]
Low [Ca2+]
Figure 11.11

53. Many G-proteins
Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways
ATP
GTP
cAMP
Protein
kinase A
Cellular responses
G-protein-linked
receptor
Adenylyl
cyclase
G protein
First messenger
(signal molecule
such as epinephrine)
Figure 11.10

54. Cyclic AMP Cyclic AMP (cAMP) Is made from ATP Figure 11.9 O –O N O POH
CH2
NH2
ATP
Ch2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

55. Epinephrine  Glycogen Breakdown
The benefit in signal pathways with multiple steps
Can amplify the signal and contribute to the specificity of the response
Epinephrine  Glycogen Breakdown

56. Response to signal
Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription
Note that more than one response can result from the reception of a single ligand

57. Response can = gene transcription (expression)
Regulate genes by activating transcription factors that turn genes on or off
Reception
Transduction
Response
mRNA
NUCLEUS
Gene P
Active
transcription
factor
Inactive
DNA
Phosphorylation
cascade
CYTOPLASM
Receptor
Growth factor
Figure 11.14

58. Termination of the Signal
Signal response is terminated quickly
By the reversal of ligand binding