1. Bell Ringer 12/16 Respond to the following in your notes:
Name and describe the 4 types of cell signaling.
Define “ligand” and “receptor protein” in the context of cell signaling.
Define quorum sensing, neurotransmitters, morphogenes, and plasmodesmata in the context of cell signaling.

2. #3
Quorum sensing: Used by bacteria to determine the density of their population via ligand concentration.
Neurotransmitters: Ligands released from the axon of one nerve cell to the dendrite of another
Morphogens: Ligands produced from a central source early in development that diffuse through tissues creating a concentration gradient that provides spatial reference for developing cells
Plasmodesmata: Channels that form between plant cells that directly connect their cytoplasm

3. Today’s Agenda:
Review Model 1 from “Signal Transduction Pathways” POGIL
Complete POGIL/check BS pages
Lecture on Ch. 11
Intro to project
YouTube video on Immune System?

4. Signal Transduction Pathways POGIL
Objectives:
List and describe the 4 steps in any signal transduction pathway.
Describe how amplification occurs during a signal transduction pathway.
Be able to describe the cyclic nature of inactive-active relay molecules within a cell and why it is important that the cell’s relay molecules are not always activated.

5. Cell Communication AP Biology
Chapter 11
Cell Communication
AP Biology

6. External signals  Cellular Responses
Cells use Signal transduction pathways
Convert signals OUTSIDE cell  cellular responses
Similar in microbes and mammals, suggesting an early origin

7. Why do cells use chemical signals?
To communicate without physical contact
Communication distant can be small OR large
Why study cell communcation?
Allows humans to modify and change pathways, create drugs to help diseases, control diseases, agriculture production, fruit ripening, etc.
What happens when cells fail to communicate properly?
Abnormal development, diseases, cancer, death

8. Chemical Signals Signal molecules (ligand)
Cells communicate through chemical messengers
Signal molecules (ligand)
growth factors
neurotransmitters
hormones (lipids)
peptides (small proteins)
Lipid soluble and insoluble

9. In local (short distance) signaling, cells may communicate via direct contact
Cell-cell recognition. Two cells in an animal may communicate
by interaction between molecules protruding from their
surfaces.

10. Both animals and plants have cell junctions that allow molecules
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
Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.

11. Bacteria & Cell-to-Cell Communcation
Quorum sensing (short distance communication)
Bacteria secrete chemical signal  helps bacteria coordinate behavior
Regulation of gene expression in bacteria in response to external stimuli.
Method used in response to population density

12. diffuses across synapse 2 types of Local signaling
Usually, multicellular organisms communicate using local regulators
Paracrine signaling.
Secreting cell acts on nearby target cells by discharging molecules of a local regulator (i.e. growth factor) into extracellular fluid.
Synaptic signaling
A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.
Local regulator
diffuses through
extracellular fluid
Target cell
Secretory
vesicle
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across synapse
Target cell is stimulated
2 types of Local signaling
Figure 11.4 A B

13. Long-distance signaling
In long-distance signaling
Both plants and animals use hormones
Hormone travels
in bloodstream
to target cells
Animal 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

14. 3 Stages of Cell Signaling
Earl W. Sutherland
Discovered how the hormone epinephrine acts on cells
Sutherland suggested that cells receiving signals went through 3 processes
Reception
Transduction
Response

15. Relay molecules in a signal transduction pathway
Overview of cell signaling
EXTRACELLULAR
FLUID
Receptor
Signal
molecule
Relay molecules in a signal transduction pathway
Plasma membrane
CYTOPLASM
Activation
of cellular
response
Figure 11.5
Reception 1
Transduction 2
Response 3

16. STEP #1: Reception
A signal molecule binds to a receptor protein  receptor changes shape
Binding between signal (called ligand) & receptor protein is highly specific
Changing shape  initiates transduction of the signal

17. Receptors 1st Type of Receptors Found in “target” cells
2 types/ locations
1. cell membrane (most abundant) called plasma membrane receptors
1st Type of Receptors

18. Plasma membrane receptors
Chemical signal for these receptors can NOT pass THROUGH membrane…so it needs to be hydrophilic. WHY?

19. 2nd type of Receptors 2. inside cell called intracellular receptors
Found in cytoplasm or nucleus
Chemical signal needs to pass THROUGH membrane…so it needs to be hydrophobic. WHY?

20. Intracellular receptors (con’t)
Signal molecules that are small or hydrophobic
WHY???
They can easily cross the plasma membrane
Ex: lipid soluble steriod/hormones (such as testosterone)

21. Specific Examples of Receptors Involved in Cell Communication

22. New protein for MALE development
Example #1: Intracellular receptor
Ex: Steroid hormones
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasma
membrane
Hormone-
receptor
complex
New protein for MALE development
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

23. Example #2, 3, 4: Cell Membrane Receptors
There are 3 main types of membrane receptors
G-protein-linked
Tyrosine kinases
Ion channel
Names based on how they work!

24. 1. G-protein-linked receptors
G-Protein = short for guanine nucleotide (GTP)-binding proteins
Ex: used in embryonic development, growth, smell, vision, over 60% of medications used today work by influencing G-protein pathways

25. G-protein-linked receptors
All G-protein-linked receptors have similar structure regardless of the organism in which they are found
Made of alpha-helices
Signal-binding site on outside of cell
G-protein-interacting site on inside of cell
Ex: epinephrine

27. 2. Tyrosine kinase Receptor
Signal molecule
Signal-binding sitea
CYTOPLASM
Tyrosines
Signal molecule
Helix in the
Membrane
Tyr
Dimer
Receptor tyrosine kinase proteins (inactive monomers) P
Cellular response 1
Inactive relay proteins
Activated relay proteins
Cellular response 2
Activated tyrosine-
kinase regions
(unphosphorylated
dimer)
Fully activated receptor
tyrosine-kinase
(phosphorylated
6 ATP ADP
Figure 11.7
Ex: used cell growth and development, reproduction

28. Part of the Tyrosine Kinase receptor on cytoplasmic side serves as an enzyme
Catalyzes transfer of Pi’s from ATP to amino acid Tyrosine on substrate

29. Ex: used in nervous system
Cellular response
Gate open
Gate close
Ligand-gated
ion channel receptor
Plasma Membrane
Signal molecule (ligand)
Gate closed
Ions
3. Ion channel receptors
Ex: used in nervous system

30. STEP #2: Transduction (converting the signal)
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

31. Signal Transduction Pathways
At each step in a pathway
signal is transduced (converted) into a different form USUALLY a conformational change in a protein using…
Protein Phosphorylation and Dephosphorylation

32. Phosphatase enzymes then remove the phosphates
In this process
A series of protein kinases add a phosphate to the next one in line, activating it
VERY IMPORTANT ~2% of our genes
Single cell has 100’s of different kinds of kinases (substrate specific)
Phosphatase enzymes then remove the phosphates

33. A phosphorylation cascade: like a Pi relay!!
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

34. Small Molecules and Ions act as Second Messengers
Are small, nonprotein, water-soluble molecules or ions
Ex: cAMP (cyclic AMP), Ca2+, IP3

35. Cyclic AMP Cyclic AMP (cAMP)
Is made from ATP by adenylyl cyclase (but cAMP is short lived!)
Figure 11.9 O –O N O P OH
CH2
NH2
ATP
Ch2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

36. Many G-proteins Cellular responses
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)
CAFFEINE BLOCKS cAMP  AMP BY PHOPHODIESTERASE SO cAMP LEVELS REMAIN HIGH
Figure 11.10

37. Other Secondary Messagers…
Inositol triphosphate (IP3)
Triggers increase in calcium ions in the cytosol by inducing the release of Ca+2 from the ER
Calcium (Ca+2)
Ex: involved in muscle contractions

38. Figure 11.12 3 2 1 4 6 5 EXTRA- CELLULAR FLUID Signal molecule
IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open. 4
The calcium ions
activate the next
protein in one or more
signaling pathways. 6
Calcium ions flow out of
the ER (down their con-
centration gradient), raising
the Ca2+ level in the cytosol. 5
DAG functions as
a second messenger
in other pathways.
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRA-
CELLULAR
FLUID
Signal molecule
(first messenger)
G protein
G-protein-linked
receptor
Various
proteins
activated
Endoplasmic
reticulum (ER)
Phospholipase C
PIP2
IP3
(second messenger)
DAG
Cellular response
(muscle
contraction)
GTP
Ca2+
(second
messenger)
IP3-gated
calcium channel
Figure 11.12

39. Cell signaling leads to:
STEP #3: Response
Cell signaling leads to:
regulation of cytoplasmic activities or
nuclear activities
Ex: transcription
DNA  mRNA

40. Cytoplasmic response to a signal
Glucose-1-phosphate (108 molecules)
Glycogen
Active glycogen phosphorylase (106)
Inactive glycogen phosphorylase
Active phosphorylase kinase (105)
Inactive phosphorylase kinase
Inactive protein kinase A
Active protein kinase A (104)
ATP
Cyclic AMP (104)
Active adenylyl cyclase (102)
Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Response
Reception
Signal Amplification
Each protein in a signaling pathway
Amplifies (continues) signal by activating multiple copies of next component in the pathway
Can be many or few proteins in cascasde
Figure 11.13

41. Other pathways
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

42. Pathway branching and “cross-talk”
Further help the cell coordinate incoming signals
Response 1
Response 4
Response 5
Response 2 3
Signal molecule
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
Activation or inhibition
Receptor
Relay molecules
Figure 11.15

43. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Can increase the signal transduction efficiency
Signal molecule
Receptor
Scaffolding protein
Three different protein kinases
Plasma membrane
Figure 11.16

44. Termination of the Signal
Signal response is terminated quickly
By the reversal of ligand binding
INACTIVE- TURNED “OFF”
ACTIVE- TURNED
“ON”

45. When things go wrong… Diabetes Heart disease
Neurological or autoimmune disorders
Cancer
Death (ex: from neurotoxins, poisons, pesticides)

46. Great tutorial to use to study…