1. Chapter 11
Cell Communication

2. Cell-to-cell communication
Is absolutely essential for multicellular organisms
Biologists have discovered some universal mechanisms of cellular regulation
cells most often communicate with other cells by chemical signals

3. Concept 11.1: External signals are converted into responses within the cell

4. Signal transduction pathways
Convert signals on a cell’s surface into cellular responses
Are similar in microbes and mammals, suggesting an early origin
Scientists think signaling mechanisms 1st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants

5. Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment.
Correct and appropriate signal transduction processes are generally under strong selective pressure.
Single-Celled Organisms
Multicellular Organisms
Environmental response
Coordination of Activities
Quorum sensing
How epinephrine is linked to glycogen breakdown

6. Communication Among Bacteria
quorum sensing: bacteria release small molecules detected by like bacteria: gives them a “sense” of local density of cells
allows them to coordinate activities only productive when performed by given # in synchrony
ex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)

7. Biofilm Developing

8. Biofilm Development

9. Cells can communicate with each other through direct contact with other cells or from a distance via chemical signaling.

10. Direct Contact Communication
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. Direct Contact Communication
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
Cells in a multicellular organism Communicate via chemical messengers
Paracrine signaling
local signaling cells send messages to local regulator cells
synaptic signaling
action potential travels thru cell membrane of neuron triggering exocytosis of neurotransmitter when at axon, NT travels in synapse to receptor site

13. diffuses across synapse
Communicate using local regulators that target cells in the vicinity of emitting cell.
(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.
(b) 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
is stimulated
Local signaling
Figure 11.4 A B

14. Long Distance Signaling
Endocrine signaling
specialized cells release hormone molecules into vessels of the circulatory system to target cells in other parts of the body
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
Figure 11.4 C

15. 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

16. 3 Stages of Cell Signaling
Reception
target cell’s detection of the signal
Transduction
receptor protein changes converting signal to a form that can bring about specific cellular response via a signal transduction pathway
Response
activation of cellular response

17. 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

18. The signal molecule (ligand) and receptor are highly specific
Signaling begins with the recognition of a chemical messenger by a receptor protein
The signal molecule (ligand) and receptor are highly specific
ex. peptides (short AA chains linked by peptide bonds)
A conformational change in a receptor
Is often the initial transduction of the signal

19. Intracellular Receptors
Are cytoplasmic or nuclear proteins
Signal molecules that are small or hydrophobic
And can readily cross the plasma membrane use these receptors

20. Receptors in the Plasma Membrane
There are three main types of membrane receptors
G-protein-linked receptors
Receptor Tyrosine kinases
Ligand-gated ion channels

21. G-protein-linked receptors
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

22. Receptor tyrosine kinases
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

23. Ion channel receptors in cytoplasm or nucleus of target cells
Cellular response
Gate open
Gate close
Ligand-gated
ion channel receptor
Plasma Membrane
Signal molecule (ligand)
Figure 11.7
Gate closed
Ions
in cytoplasm or nucleus of target cells
hydrophobic or very small ligands
examples
steroid hormones & thyroid hormones of animals

24. ION CHANNEL RECEPTORS Ligand-Gated Ion Channels
ion crosses membrane & enters cytoplasm  transduction pathway leading to a response

25. INTRACELLULAR RECEPTORS
In cytoplasm or nucleus of target cell
hydrophobic signaling molecules
Steroid hormones
Bind 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

26. Turning on Genes Testosterone (steroid hormone)
special proteins called transcription factors control which genes are turned on
example:
Testosterone (steroid hormone)
its activated receptor acts as transcription factor that turns on specific genes
thus activated receptor carries out transduction of the signal

27. Transduction: cascades of molecular interactions relay signals from receptors to target molecules in the cell

28. Signal Transduction Pathways
Signal transduction is the process by which a signal is converted to a cellular response
Multistep pathways
Can amplify a signal
Provide more opportunities for coordination and regulation
At each step in a pathway
The signal is transduced into a different form, commonly a conformational change in a protein

29. Protein Phosphorylation and Dephosphorylation
Many signal pathways
Include phosphorylation cascades
cascades relay signals from receptors to cell targets , amplifying the signal, resulting in a response by the cell.
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
VIDEO

30. 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

31. Small Molecules and Ions as Second Messengers
The first messenger is the extracellular signal molecule that binds to the membrane receptor
Second messengers are essential to the function of the cascade
Are small, nonprotein, water-soluble molecules or ions
readily spread throughout the cell via diffusion
Examples:
Ligand-gated ion channels
cyclic AMP
cyclic GMP
calcium ions and IP3

32. Cyclic AMP (cAMP)
carries a signal initiated by epinephrine from the PM of a liver/muscle cell into the interior of the cell where it initiates glycogen breakdown
Figure 11.9 O –O N O P OH
CH2
NH2
ATP
Ch2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

33. Epinephrine (adrenaline) binds to a receptor on the PM on a liver cell, elevating the concentration of cAMP inside the cell, activating adenylyl cyclase
adenylyl cyclase converts ATP into lots of cAMP as a result
cAMP doesn’t last if epinephrine isn’t present because of phosphodiesterase, it coverts cAMP into AMP
more epinephrine is needed to boost amount of cAMP in cytosol

34. Many G-proteins
Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways
video
Figure 11.10

35. Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription

36. Cytoplasmic and Nuclear Responses
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
In the cytoplasm
Signaling pathways regulate a variety of cellular activities
regulating the activity of the enzyme

37. Epinephrine
Same receptor
Different response

38. Circulatory system hypothalamus Liver Lungs Intestines Heart Kidneys
Adrenal gland
releases adrenaline (epinephrine)
Circulatory system
hypothalamus
Hypothalamus sends signal to muscles and to adrenal gland (adrenal medulla) on the kidneys. It gives off adrenaline. Epinephrine. It goes to proteins on surface of liver cells. Triggering a signal transduction pathway to glycogen to make glucose. Glucose is our energy supply to quickly break down glucose for ATP throughout body. Epinephrine goes throughout all of body vis circulatory system. Speeding up breathing in lungs, speeding up heart beat triggering signal transduction very similar as that in liver, but different response- doesn’t break down glycogen, rather speeds up the heart. Digestive system- epinephrine slows down digestion.
Liver
Lungs
Intestines
Heart

39. Other pathways
Regulate genes by activating transcription factors that turn genes on or off
regulate the synthesis of enzymes or proteins, unlike epinephrine
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasma
membrane
Hormone-
receptor
complex
New protein
Figure 11.6
Reception
Transduction
Response
mRNA
NUCLEUS
Gene P
Active
transcription
factor
Inactive
DNA
Phosphorylation
cascade
CYTOPLASM
Receptor
Growth factor
Figure 11.14

40. Fine-Tuning of the Response
Signal pathways with multiple steps
Can amplify the signal and contribute to the specificity of the response

41. Signal Amplification Each protein in a signaling pathway
Amplifies the signal by activating multiple copies of the next component in the pathway
Epinephrine triggered pathways: each adenylyl cyclase catalytic event forms more cAMP molecules and each protein kinase phosphorylation makes more of the next kinase; thus amplyfying all the products in transduction

42. The Specificity of Cell Signaling
The different combinations of proteins in a cell
Give the cell great specificity in both the signals it detects and the responses it carries out

43. 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

44. 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

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

46. Real Applications Fight or Flight
Hypothalamus sends signal to muscles and to adrenal gland (adrenal medulla) on the kidneys. It gives off adrenaline. Epinephrine. It goes to proteins on surface of liver cells. Triggering a signal transduction pathway to glycogen to make glucose. Glucose is our energy supply to quickly break down glucose for ATP throughout body. Epinephrine goes throughout all of body vis circulatory system. Speeding up breathing in lungs, speeding up heart beat triggering signal transduction very similar as that in liver, but different response- doesn’t break down glycogen, rather speeds up the heart. Digestive system- epinephrine slows down digestion.