Professional Documents
Culture Documents
06 Capturing and Using Energy 2015
06 Capturing and Using Energy 2015
06 Capturing and Using Energy 2015
Cell Communication
Cells talk to each other. Lets look at two examples before
considering how this works
1. Chemotaxis individual Dictyostelium amoebae moving
towards a chemoattractant chemical
2. Quorum sensing individual bacteria that communicate
signals that can regulate light production or the ability to
take up DNA molecules.
Here bacteria are dark until they sense that there are enough bacteria in the
flask to form a quorum sufficient to trigger them to luminesce.
To learn more about this, watch the video by Bonnie Bassler, who is making important
discoveries about quorum sensing https://www.youtube.com/watch?v=S3BOcUrJ5Vg
or read the short article by Jessica Marshall that Ill post on line.
9. Cell Communication
DNA
molecule
Basic cell signaling requires a (1) signaling molecule (ligand), (2) a receptor,
and (3) molecules inside the cell that transduce the signal and make the cell
respond to the signal.
Signaling
molecule
Receptor
We are familiar with cell signaling that allows cells in our bodies to communicate with other cells. Do free-living single
cells, such as bacteria or amoeba, signal each other or did signaling evolve when multicellular organisms developed?
Explain your answer.
All of the genes in a cell are simply parts of a sequence of nucleotides in a DNA molecule. Can cells incorporate DNA
from other intact or broken cells? Explain your answer and provide examples that support your answer. Your
examples may include examples from previous portions of this course.
The synthesis of cell-surface hormone receptors is regulated by the expression of genes that code for these receptors.
Assume that a receptor gene is expressed and is being translated by a ribosome. Describe the pathway by which that
receptor protein is eventually displayed on the surface of the plasma membrane in an orientation that will allow the
receptor to bind an extracellular hormone.
If all cells in a body are exposed to every hormone released into the bloodstream, why do some cells respond to a
specific hormone while other cells ignore the hormone?
Plasma membrane
Extracellular
fluid
Receptor activation
Cytoplasm
Signal transduction
Response
The signal is
transmitted to the
interior of the cell by
a signal transduction
pathway.
a. Endocrine signaling
The cell
responds, for
example, by
activating an
enzyme or
turning on
transcription of
a gene.
Termination
The response
is terminated
so that new
signals can
be received.
Signaling
molecule
b. Paracrine signaling
Plasma
membrane
Acetylcholine
binding opens
ion channels,
allowing Na+ to
flow into the
muscle cell.
Acetylcholine
Nerve cell
Muscle cell
Open
Na+
Closed
Binding site
c. Autocrine signaling
Direct contact
signaling
Unclotted
blood
Fibroblast
Clotted
blood
Plasma
Serum
There are a number of different mechanisms by which cells release and receive signals. Give an example of each of
the following or describe the mechanisms by which they work:
endocrine signaling
paracrine signaling
direct contact between animal cells
direct contact between plant cells
One difficulty of stimulating mammalian cells to grow in culture is that even if you provide them with the food
they need, they do not produce a greater number of cells. Describe an experiment in which growth factors
that stimulate cell growth were identified.
You have a population of cells that respond to growth factors and will reproduce
at a reasonable pace, shown in this figure.
Now, suppose that you obtain a population of these cells that will not reproduce,
even though you add the growth factors and plenty of food.
Assuming that the growth factor stimulates cells by binding to an extracellular
receptor, propose a reason why the non-reproducing cells are no longer
responsive to the growth factors.
a. Cell-surface receptor
Polar signaling
molecule
Extracellular
domain
Transmembrane
domain
Cytoplasmic
domain
Plasma
membrane
Ligand-binding site
Activated receptor
Polar signaling
molecules cannot
cross the plasma
membrane and
rely on cellsurface receptors.
Nucleus
DNA
b. Intracellular
receptor
Small, nonpolar
signaling molecule
Activated receptorsignal
complex
Small nonpolar
signaling molecules
can freely pass
through the plasma
membrane and
activate cytoplasmic
receptors.
Intracellular receptors
Cell signaling requires a signal molecule (ligand) and a receptor. Types of ligands that function as hormones in
humans include steroids and peptides.
a. What chemical properties distinguish steroid and peptide hormones?
b. Where are the receptors located for steroid and for peptide hormones?
Compare the pathways by which extracellular receptor is synthesized and positioned on the plasma membrane with
the pathway required for synthesis of the steroid hormone receptor.
Suppose the steroid receptor mRNA had a signal sequence to target the protein to the ER. Describe what you think
might happen to that receptor and explain your answer.
b. G protein-coupled receptor
Ligand
Receptor
G protein
GDP
GTP
Inactive
Active
Signaling
pathways
Response
c. Receptor
kinase
Phosphate
group
Response
b. Ligand-gated ion
channel
Ions
Response
Inactive
effector
Ligand
Receptor
G protein
GDP
GTP
GDP
Active
effector
Second
messengers
GTP
Response
Inactive
adenylyl
cyclase
Adrenaline
Receptor
GDP
Activated
adenylyl
cyclase
Adrenaline
receptor
Protein
kinase A
GTP
ATP
Active
G protein
cAMP
Inactive
Active
10
Adrenaline
Activated
receptor
Amplification
GTP
Active subunit
of G protein
ATP
GTP
cAMP
ATP
cAMP
ATP
cAMP
Amplification
Inactivated protein
kinase A
Activated protein
kinase A
Amplification
GTP
ATP
ADP
GTP
Protein
kinase A
The signal molecule
adrenaline detaches
from the receptor after
a certain amount of
time, inactivating the
receptor so that it can
no longer bind to and
activate the G protein.
Activated
adenylyl
cyclase
Inactive
ATP
cAMP
Inactive
Phosphatase
Active
Active
Phosphate
group
GDP
Phosphatases remove
phosphate groups from
proteins, causing them to
become inactive.
Phosphodiesterase
cAMP
AMP
Enzymes in the cytosol specifically
degrade cAMP which stops the
phosphorylation and activation of
target proteins by PKA.
11
Signaling
molecules
The attached
phosphate groups
provide binding sites
for intracellular
signaling proteins.
Cytoplasmic
signaling
proteins
Phosphate
group
Inactive receptor
Dimerization
Active receptor
Signaling
molecule
Active receptor
Activated Ras
signaling protein
GTP
Inactive receptor
Active receptor
12
Inactive
kinase 1
Active
kinase 1
GTP
ATP
ADP
Active
kinase 2
ATP
ADP
Active
kinase 3
Changes
in gene
expression
Nucleus
Transcription regulators
Plasma
membrane
Acetylcholine
binding opens
ion channels,
allowing Na+ to
flow into the
muscle cell.
Acetylcholine
Nerve cell
Muscle cell
Open
Na+
Closed
Binding site
Botulism toxin contains several proteins, one of which can enter a nerve cell and prevent fusion of a synaptic
vesicle with the plasma membrane. One of these is the Botox that doctors inject into patients to prevent
wrinkles. Why does Botox treatment prevent wrinkling?
13
G-protein
receptor
Signal
molecule
Chloride ions
leave cell
CFTR
GDP
GTP
Adenylyl
cyclase
Phosphorylate
and activate
CFTR
cAMP
ATP
Activate Protein
kinase A
Important:
Chloride is only released
when the signal molecule
activates the G-protein
receptor.
G-protein
receptor
CFTR
GDP
CFTR
channel
closes
GTP
cAMP
ATP
Phosphodiesterase
PkA no
longer
active
AMP
G-protein
receptor
CFTR
GDP
GTP
Adenylyl
cyclase
cAMP
ATP
Phosphorylate
and activate
CFTR
Activate Protein
kinase A
14
Chloride ions
leave cell
G-protein
receptor
CFTR
GDP
GTP
Adenylyl
cyclase
Phosphorylate
and activate
CFTR
cAMP
ATP
Activate Protein
kinase A
Florida
Haiti
15
16
Cholera toxin, released from Vibrio cholerae bacteria, induces diarrhea and dehydration. Infected individuals die
because they are dehydrated, due to water loss from the bloodstream. Water is lost because chloride channels that
bind and are activated by cyclic AMP release chloride ions into the intestine. This increase in salt (chloride and
sodium ions) draws water (by osmosis) out of the bloodstream and into the intestine, resulting in diarrhea. Cholera
toxin acts on the G-protein and prevents GTP hydrolysis.
a. Sketch the process by which the binding of a bacterial protein opens chloride channels. (Hint chloride
channels are ligand-gated ion channels).
b. Cholera toxin blocks GTP hydrolysis by the G protein. Why does it induce diarrhea?
c. Based on your knowledge of osmosis, how can osmosis induce movement of water from tissue into the
intestine?
d. How can infection of a human with Vibrio cholera cause diarrhea?
d. Without proposing antibiotics, to kill bacteria, or miracle drugs, to block the action of cholera toxin, propose a
simple and inexpensive method that might be (is) used to treat patients infected with Vibrio cholerae bacteria.
Receptor tyrosine kinases are important for many signaling activities some of which are associated with mammalian
growth and cell division. When the receptor binds a signaling molecule, the receptors dimerize (two receptors bind to each
other) and activate a tyrosine kinase.
a. What kind of molecule is a kinase?
b. What does a protein kinase do?
c. What is tyrosine?
Compare the functions of protein kinases and protein phosphatases. Give one example from this lecture to
illustrate their importance in cells..
One of the key properties of signal transduction pathways is the ability of each signaling molecule in the pathway to be
turned on or turned off.
Consider each of the following pathways and identify, for each step in the pathway,
(a) the components that are turned on,
(b) the mechanism or molecule that activates each molecule,
(c) the mechanism or molecule that inactivates the activated molecule
(d) what would happen to the process if any one of the steps were not able to be inactivated.
Pathway:
1. A pathway in which a ligand stimulates a G-protein coupled receptor to open a CFTR (cystic fibrosis
channel protein) channel to allow chloride ions to diffuse out of a cell. Your answer should include the
mechanism by which the CFTR channel is opened (within the limits of what we discussed in lecture), the
mechanism by which the CFTR channel would be closed, and what would happen if GTP could not be
hydrolyzed by G-proteins associated with this process. (This question and answer should be similar to the first
question in this set)
2. A pathway by which the binding of a single epinephrine molecule to a cell-surface G-protein receptor can
induce the release of 100,000,000 glucose molecules from stored glycogen molecules. Your answer should
include the steps by which the production of glucose from glycogen occurs and what happens if epinephrine
is no longer bound to the receptor.
Types of G proteins
There are two major classes of G proteins
Monomeric G proteins
Heterotrimeric G proteins
What is a difference between a monomeric and a
heterotrimeric G protein?
All are inactive with GDP bound and active with GTP bound
17
Heterotrimeric G proteins
Composed of 3 protein
subunits - , ,
Rho
Rab
Ran
Arf
18
Scaffold proteins are found in a number of cells, With regard to signaling, what might be a function of a
scaffolding protein?
19