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AP Biology
I think she meanta different kind of
cellular communication…
Chapter 11
Cellular Communication
Don’t you get it? It’s what I meant to say, not
what I really said!…
AP Biology
External signals are converted to responses within the cell
© 2011 Pearson Education, Inc.
Exchange of mating
factors
Receptor
factor
factor
Yeast cell,mating type a
Yeast cell,mating type
Mating
New a/ cell
1
2
3
a
a
a/
Yeast has two mating types,
a and Cells locate each other via
secreted factors
Signal Transduction Pathway
series of steps that convert a
signal on a cell’s surface into
a specific cellular response.
a factor
AP Biology
Pathway similarities suggest ancestral signaling molecules evolved in prokaryotes and later modified in eukaryotes.
Signal molecule concentration allows bacteria to sense population density.
© 2011 Pearson Education, Inc.
Common trait, common ancestry…
AP Biology
Individualrod-shaped
cells
Spore-formingstructure
(fruiting body)
Aggregation in progress
Fruiting bodies
1
2
3
0.5 mm
2.5 mm
Figure 11.3
AP Biology
Long-Distance and Local Signaling Cells in a multicellular organism
communicate by chemical messengers. Animal and plant cells use
cell junctions directly
connect cytoplasm of adjacent
cells
And
Local signaling communication by direct contact,
or by cell-cell recognition
© 2011 Pearson Education, Inc.
Plasma membranes
Gap junctionsbetween animal cells
Plasmodesmatabetween plant cells
(a) Cell junctions
(b) Cell-cell recognition
AP Biology
Long-Distance Signaling
plants and animals use chemicals called hormones
The ability of a cell to respond to a signal depends on presence of the receptor specific to that signal
© 2011 Pearson Education, Inc.
Long-distance signaling
Endocrine cell Bloodvessel
Hormone travelsin bloodstream.
Target cellspecifically
binds hormone.
(c) Endocrine (hormonal) signaling
AP Biology
Local Signaling messenger molecules that travel only short distances
© 2011 Pearson Education, Inc.
Target cell
Secretingcell
Secretoryvesicle
Local regulatordiffuses through
extracellular fluid.
(a) Paracrine signaling (b) Synaptic signaling
Electrical signalalong nerve cell
triggers release ofneurotransmitter.
Neurotransmitter diffuses across
synapse.
Target cellis stimulated.
AP Biology
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
© 2011 Pearson Education, Inc.
AP Biology© 2011 Pearson Education, Inc.
Animation: Overview of Cell Signaling Right-click slide / select “Play”
AP Biology
Figure 11.6-1
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception
Receptor
Signalingmolecule
1
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception Transduction
Receptor
Signalingmolecule
Relay molecules in a signal transductionpathway
21
Plasma membrane
EXTRACELLULARFLUID
CYTOPLASM
Reception Transduction Response
Receptor
Signalingmolecule
Activationof cellularresponse
Relay molecules in a signal transductionpathway
321
Reception: signaling molecule binds to receptor protein, causing conformation change. 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
AP Biology
Types of Receptors in the Plasma Membrane
Water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane
There are three main types of membrane receptors
G protein-coupled receptorsReceptor tyrosine kinasesIon channel receptors
© 2011 Pearson Education, Inc.
AP Biology© 2011 Pearson Education, Inc.
G protein-coupled receptors (GPCRs)
• Largest family of cell-surface receptors.
• Works with the help of a G protein (Guanine nucleotide-
binding proteins) - acts as an on/off switch.
“off” when bound to GDP (Guanine diphosphate)
“on” when bound to GTP (Guanine triphosphate)
You know what turns me on!
…and off!
AP Biology
Figure 11.7a
G protein-coupled receptor
Signaling molecule binding site
Segment thatinteracts with
G proteins
AP Biology
Figure 11.7b
G protein-coupledreceptor
21
3 4
Plasmamembrane
G protein(inactive)
CYTOPLASMEnzyme
Activatedreceptor
Signalingmolecule
Inactiveenzyme
Activatedenzyme
Cellular response
GDPGTP
GDPGTP
GTP
P i
GDP
GDP
http://www.youtube.com/watch?
v=4dUJ5GNpfrA&feature=endscreen&NR=1
AP Biology
Receptor tyrosine kinases (RTKs) receptors that attach phosphates to tyrosines
A receptor tyrosine kinase can trigger
multiple signal transduction pathways at once Abnormal functioning of RTKs is associated
with many types of cancers
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.7c
Signalingmolecule (ligand)
21
3 4
Ligand-binding site
helix in themembrane
Tyrosines
CYTOPLASM Receptor tyrosine kinase Proteins (inactive monomers)
Signalingmolecule
Dimer
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
P
P
P
P
P
P
Activated tyrosinekinase regions
(unphosphorylateddimer)
Fully activatedreceptor tyrosine
kinase(phosphorylated
dimer)
Activated relayproteins
Cellularresponse 1
Cellularresponse 2
Inactiverelay proteins
6 ATP 6 ADP
AP Biology
Ligand-gated ion channel receptors acts as gates when the receptors change 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
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.7d
Signalingmolecule (ligand)
21 3
Gate closed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed
AP Biology
Intracellular Receptors Intracellular receptor proteins are found in
the cytosol 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
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.9-1
Hormone(testosterone)
Receptorprotein
Plasmamembrane
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Hormone(testosterone)
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
EXTRACELLULARFLUID
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
I like this Testosterone
stuff!
AP Biology
Figure 11.9-5
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
1.
2.
3.
4.
5.
6.
AP Biology
Transduction:
Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction 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
© 2011 Pearson Education, Inc.
AP Biology
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 conformational change in a protein.
© 2011 Pearson Education, Inc.
AP Biology
Protein Phosphorylation and Dephosphorylation
In many pathways, the signal is transmitted by a cascade of protein phosphorylations.
Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation.
© 2011 Pearson Education, Inc.
AP Biology
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 or up or down, as required.
© 2011 Pearson Education, Inc.
AP Biology
Activated relaymolecule
Phosphorylation cascade
Inactiveprotein kinase
1 Activeprotein kinase
1
Activeprotein kinase
2
Activeprotein kinase
3
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
ATPADP
ATPADP
ATPADP
PP
PP
PP
P
P
P i
P i
P i
P
Figure 11.10aSignaling molecule
Cellularresponse
AP Biology
Small Molecules and Ions as Second Messengers
“First messenger” - extracellular signal
molecule (ligand) binds to the receptor. Second messengers are small, nonprotein,
water-soluble molecules or ions that spread throughout a cell by diffusion.
ex. - Cyclic AMP and calcium ions Second messengers participate in pathways
initiated by GPCRs and RTKs
© 2011 Pearson Education, Inc.
AP Biology
Cyclic AMP• Cyclic AMP (cAMP) - widely used second
messenger.
• Adenylyl cyclase converts ATP to cAMP in response to an extracellular signal.
© 2011 Pearson Education, Inc.
Adenylyl cyclase Phosphodiesterase
Pyrophosphate
AMP
H2O
ATP
P iP
cAMP
AP Biology
Many signal molecules trigger formation of cAMP.
Components of cAMP pathways: a) G proteins
b) G protein-coupled receptors
c) protein kinases
cAMP usually activates protein kinase A, which phosphorylates various other proteins.
Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase (which shuts down cAMP production).
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.12
G protein
First messenger(signaling molecule
such as epinephrine)
G protein-coupledreceptor
Adenylylcyclase
Second messenger
Cellular responses
Proteinkinase A
GTP
ATP
cAMP
AP Biology
Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration
© 2011 Pearson Education, Inc.
Mitochondrion
EXTRACELLULARFLUID
Plasmamembrane
Ca2
pump
Nucleus
CYTOSOL
Ca2
pump
Ca2
pump
Endoplasmicreticulum
(ER)
ATP
ATP
Low [Ca2 ]High [Ca2 ]Key
AP Biology
Figure 11.13
Mitochondrion
EXTRACELLULARFLUID
Plasmamembrane
Ca2
pump
Nucleus
CYTOSOL
Ca2
pump
Ca2
pump
Endoplasmicreticulum
(ER)
ATP
ATP
Low [Ca2 ]High [Ca2 ]Key
AP Biology
A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol
Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
© 2011 Pearson Education, Inc.
AP Biology© 2011 Pearson Education, Inc.
Animation: Signal Transduction Pathways Right-click slide / select “Play”
AP Biology
Figure 11.14-3
G protein
EXTRA-CELLULAR
FLUID
Signaling molecule(first messenger)
G protein-coupledreceptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gatedcalcium channel
Endoplasmicreticulum (ER)
CYTOSOL
Variousproteinsactivated
Cellularresponses
Ca2
(secondmessenger)
Ca2
GTP
AP Biology
Nuclear and Cytoplasmic Responses
Signal transduction pathway leads to regulation of one or more cellular activities
Response may occur in the cytoplasm or 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 in the signaling pathway may function as a transcription factor.
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.15
Growth factor
Receptor
Reception
Transduction
CYTOPLASM
Response
Inactivetranscription
factor
Activetranscription
factor
DNA
NUCLEUS mRNA
Gene
Phosphorylationcascade
P
AP Biology
Other pathways regulate the activity of enzymes rather than their synthesis
© 2011 Pearson Education, Inc.
Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape
AP Biology
Fine-Tuning of the Response
There are four aspects of fine-tuning to consider
Amplification of the signal Specificity of the response Overall efficiency of response, enhanced
by scaffolding proteins Termination of the signal
© 2011 Pearson Education, Inc.
AP Biology
Signal Amplification
Enzyme cascades amplify the cell’s response.
At each step, the number of activated products is much greater than in the preceding step.
© 2011 Pearson Education, Inc.
AP Biology
The Specificity of Cell Signaling and Coordination of the Response
Different kinds of cells have different collections of proteins
These different proteins allow cells to detect and respond to different signals
Even the same signal can have different effects in cells with different proteins and pathways
Pathway branching and “cross-talk” further help the cell coordinate incoming signals
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.18
Signalingmolecule
Receptor
Relay molecules
Response 1
Cell A. Pathway leadsto a single response.
Response 2 Response 3 Response 4 Response 5
Activationor inhibition
Cell B. Pathway branches,leading to two responses.
Cell C. Cross-talk occursbetween two pathways.
Cell D. Different receptorleads to a different
response.
AP Biology
Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes Scaffolding proteins are large relay proteins
to which other relay proteins are attached Increase the signal transduction efficiency
by grouping together proteins involved in the same pathway
May also help activate some of the relay proteins
© 2011 Pearson Education, Inc.
AP Biology
Figure 11.19
Signalingmolecule
Receptor
Plasmamembrane
Scaffoldingprotein
Threedifferentproteinkinases
AP Biology
Termination of the Signal
Inactivation mechanisms are an essential aspect of cell signaling.
If ligand concentration falls, fewer receptors will be bound.
Unbound receptors revert to an inactive state.
© 2011 Pearson Education, Inc.
AP Biology
Apoptosis integrates multiple cell-signaling pathways
Apoptosis is programmed or controlled cell suicide
Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells
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AP Biology
Apoptotic Pathways and the Signals That Trigger Them
Caspases -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
© 2011 Pearson Education, Inc.
AP Biology
Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals
Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers
© 2011 Pearson Education, Inc.
Interdigital tissueCells undergoing
apoptosisSpace between
digits1 mm