Download Cell Signaling PPT - Fairfield Public Schools

Cell-Cell Communication
Overview: Cellular Signaling
• Cells communicate with each other via chemical
signals.
• For example, the fight-or-flight response is
triggered by a signaling molecule called
epinephrine
• Cell-to-cell communication is essential for both
multicellular and unicellular organisms
• Biologists have discovered some universal
mechanisms of cellular communication
© 2011 Pearson Education, Inc.
Cell Signaling by Multicellular Organisms
• Coordinates activities within individual cells to
support the function of the organism as a whole
• Examples:
– Response to DNA damage
• Could lead to expression of mutant proteins and
cellular dysfunction and/or cancer if unchecked
• Cell signaling pathways prevent this by activating
DNA repair enzymes or initiating programmed cell
death (apoptosis)
© 2011 Pearson Education, Inc.
Local Signaling
• In local signaling, cells within multicellular
organisms may communicate by:
– contact through the cytoplasm of adjacent cells
• cell junctions
– cell-cell contact
• Ligand on one cell binds to a receptor on an adjacent
cell
– short range signals
• Cell secretes a soluble ligand that binds to a receptor
on a nearby cell
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Local Signaling:
Cytoplasmic contact at cell junctions
Cell-cell contact between adjacent cells
involving membrane bound ligands
Short range signals involving soluble ligands
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling
Neurotransmitter
diffuses across
synapse.
Secretory
vesicle
Target cell
is stimulated.
(b) Synaptic signaling
Long-Distance Signaling
• In long distance signaling, cells within
multicellular organisms may communicate use
chemicals called hormones
– synthesized by cells in one region of the body
– travel through the bloodstream to reach their
cellular targets in other regions of the body
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Figure 11.5b
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
Signal Specificity and Cell Specialization
• Only the signaling molecule that fits the shape of a
specific receptor can trigger a response in a cell
• Mediated by shape and chemical nature of
interacting regions
• Different cell types produce different receptors
• A cell synthesizes many different kinds of receptors,
depending on conditions or stages in its life cycle
• The same signal can have different meanings for
various target cells
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The Three Stages of Cell Signaling:
(within 1 cell)
1) Reception
2) Transduction
3) Response
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Figure 11.6-1
EXTRACELLULAR
FLUID
1 Reception
Receptor
Signaling
molecule
CYTOPLASM
Plasma membrane
Figure 11.6-2
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signaling
molecule
Figure 11.6-3
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signaling
molecule
Step 1: Signal Reception
• A signaling molecule binds to a receptor
protein, causing it to change shape, and
initiating the transduction of the signal
• Most receptors are plasma membrane proteins
but some are inside of the cell
(cytoplasmic/nuclear receptors)
• The binding between a signal molecule (ligand)
and receptor is highly specific
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Cell Surface and Intracellular Receptors
Receptors in the Plasma Membrane
• There are three main types of membrane
receptors
– Ion channel receptors
– G protein-coupled (linked) receptors
– Protein kinase receptors (aka receptor
tyrosine kinases)
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Ligand-Gated Ion Channel Receptors
• A ligand-gated ion channel receptor acts as a
gate
• When a ligand binds to the receptor, the shape
changes, allowing specific ions, such as Na+ or
Ca2+, to pass into the cell through a channel in
the receptor
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Ligand-Gated Ion Channel Receptors
Signaling
molecule
Na+
Extracellular
fluid
Receptor
Cytosol
1 Ion channel is closed.
2 When signaling molecule binds to
receptor, the channel changes shape
and opens. Sodium ions enter the
cell.
Fig. 6-5a, p. 140
G Protein Linked Receptors
• A GPCR is a plasma membrane receptor that
works with the help of a G protein, located in the
cytoplasm
• Upon ligand binding the G protein is turned on by
the exchange of GDP for GTP
• The G protein then helps to transmit the
intracellular signal
© 2011 Pearson Education, Inc.
G Protein Coupled Receptors
Signaling
molecule
Receptor
G protein Enzyme
Cytosol
GDP
1 Inactive state: the three
subunits of G protein are
joined and it is bound to GDP
GTP
2 Ligand binding: receptor binds
to G protein causing GDP to be
replaced with GTP and the
separation of one subunit. This
is the active state.
Fig. 6-5b, p. 140
Protein Kinase Receptors
• PKRs are membrane receptors that also have
enzymatic activity
• transfer phosphate groups (phosphorylation)
from ATP to specific tyrosine residues on proteins
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• Abnormal functioning of PKRs is associated with
many types of cancers
© 2011 Pearson Education, Inc.
Receptor Tyrosine Kinases
Signaling
molecule (ligand)
Ligand-binding site
 helix in the
membrane
Signaling
molecule
Tyrosines
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
1
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
2
Activated relay
proteins
3
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
P Tyr
Tyr P
6
ATP
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
6 ADP
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
4
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Intracellular Receptors
• Intracellular receptors are found in the cytosol or
nucleus – most are transcription factors that
regulate expression of specific genes
• Signaling molecules are small, hydrophobic
molecules that diffuse across the membranes of
target cells
– Some combine with receptors in the cytosol, then
move into the nucleus (e.g. steroid hormones)
– Some bind to receptors already bound to DNA inside
the nucleus (e.g. thyroid hormones)
© 2011 Pearson Education, Inc.
Hormone
(testosterone)
Steroid
hormone
interacting
with an
intracellular
receptor
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
Step 2: Signal Transduction
• Cascades of molecular interactions relay
signals from receptors to target molecules
in the cell.
• Signals are relayed by:
– Protein kinases
– Second messengers
• Both of these mechanisms help to
amplify the signal inside of the cell
© 2011 Pearson Education, Inc.
Step 2: Signal Transduction
• Protein kinases help to transmit signals
through a cascade of protein phosphorylations
– Protein kinases transfer phosphate groups from
ATP to other proteins, a process called
phosphorylation
• acts like a molecular on-off switch
– The addition of phosphate groups (by
kinases)acts like an “on” switch and activates
proteins
– The removal of phosphate groups (by
phosphatases) acts like an “off” switch and deactivates proteins
© 2011 Pearson Education, Inc.
Figure 11.10
Signaling molecule
Receptor
Signal
transduction by
protein kinases
involving a
phosphorylation
cascade
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
P
Active
protein
kinase
2
PP
Pi
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
PP
Pi
Active
protein
Cellular
response
Step 2: Signal Transduction
• Second messengers
– Ions or small molecules that amplify signals
inside the cell and relay them to other signaling
or target proteins
– Ex: cyclic AMP (cAMP), inositol triphosphate
(IP3) , and calcium ions (Ca2+)
© 2011 Pearson Education, Inc.
1 Ligand binds to
Signaling molecule
Extracellular fluid
GPCR, activating (first messenger)
Adenylyl
the G protein
cyclase
Receptor G protein
and causing one
subunit to bind
to and activate
Plasma
Adenylyl
membrane
Cyclase, which
then catalyzes
Cytosol
formation of
cAMP from ATP
cAMP
2 Signal is
amplified and
relayed by the
second
messenger
cAMP
3 Response: some
cell process is
altered
cAMP
cAMP
cAMP
Protein
Protein
Protein
Alters
metabolism
Affects
gene activity
Second
messenger
Opens or closes
ion channels
Fig. 6-7, p. 143
Figure 11.14-3
EXTRACELLULAR
FLUID
Signaling pathway involving
the second messengers
2
IP
and
Ca
3
G protein
Signaling molecule
(first messenger)
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Ca2
Ca2
(second
messenger)
Cellular
responses
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
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Signal Amplification
Step 3: Response
Cell signaling leads to regulation of cellular
activity including:
•Opening or closing of ion channels
•Alteration of enzyme activity, leading to
metabolic changes
• Ex, fight or flight response
•Alteration of specific gene activity
• specific proteins made or not made in response
•Apoptosis
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Cellular Response to Signaling
Growth factor
Reception
Receptor
Cellular
Response:
Activation
of a
specific
gene by a
growth
factor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
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.
How does cell signaling trigger the
desperate flight of this gazelle?
Link
Fight or Flight Signaling Pathway
• Epinephrine (adrenaline), a hormone, is
released by the adrenal gland.
• It travels through the blood stream to reach its
target in muscle or liver cells.
• There is binds to a G protein coupled
receptor and initiates a signaling cascade
• Results in glucose release by the cells
leading to increased heart and breathing rate
Fight or Flight Signaling Pathway
Epinephrine
G protein
coupled
receptor
G protein
Extracellular fluid
Adenylyl
cyclase
Plasma
membrane
Cytosol
1
Reception of Signal
Fig. 6-9a, p. 144
Fight or Flight Signaling Pathway
Epinephrine
G protein
coupled
receptor
G protein
separates
Adenylyl
cyclase
2 Initiation of Signal Transduction
Fig. 6-9b, p. 144
Ligand:
epinephrine
G protein
coupled
Receptor
Adenylyl
cyclase
activated
Dissociation of
activated G protein
Phosphorylated
Protein kinase A
Fight or Flight
Protein Phosphorylated
protein (active)
Signaling
Pathway
Glycogen is broken down into
3
Cellular Response
Animation
glucose, which is released by the
cell. Causes increased blood flow
and heart rate as well as increased
breathing rate.
Fig. 6-9c, p. 144
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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Role of Apoptosis in
Development and Disease
• 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.
Figure 11.22
Role of Apoptosis in
Development
Interdigital tissue
Cells undergoing
apoptosis
Space between
1 mm
digits
Evolutionary History of Cell Signaling
• Similarities in cell communication among
diverse organisms suggest that the molecules
and mechanisms used in information transfer
evolved long ago
• Evidence suggests that cell communication
first evolved in prokaryotes
– Some signal transduction pathways found in
organisms as diverse as yeasts and animals
are quite similar
– Highly conserved nature suggests an
evolutionary relationship
Cellular Signaling and Development
• Cellular signaling plays a critical role in
development and maintenance of
multicellular organisms
– establishment of body axes
– cell fate decisions leading to the formation of
germ layers and organ development
– maintenance of stem cells within the body
Cellular Signaling and Disease
• Mutations that cause over- or underactive
cell signaling can result in disease
– diabetes, neurological diseases, autoimmune
diseases, cancer
• Many therapeutic drugs seek to block or
balance out over- or underactive signaling
pathways
– birth control, antihistamines, anti-psychotics,
anti-cancer drugs
Cellular Signaling and Biotechnology
• Understanding these pathways allows
scientists to modify or manipulate
biological systems and cellular physiology
–
–
–
–
Drugs to treat disease
Control of fruit ripening
Use of growth hormones in poultry, etc
Doping by athletes (EPO, HGH)
Helpful Videos/Animations:
•
AP Biology Hayescience “Cell Communication” a general overview- can go back to look at
specifics https://www.youtube.com/watch?v=XtN9YjIJhz8
•
Crash Course “Nervous System Part 3: Synapses” a general overview
https://www.youtube.com/watch?v=VitFvNvRIIY
•
Bozeman “Cell Communication” https://www.youtube.com/watch?v=xnGXItWrJ3k
•
Bozeman “Signal Transduction Pathways”
https://www.youtube.com/watch?v=qOVkedxDqQo
•
Life (your textbook): Ch. 7 animations - “Signal Transduction Pathway” & “Signal
Transduction & Cancer”
http://bcs.whfreeman.com/thelifewire9e/default.asp#542578__591101__
•
The Penguin Prof “Signal Transduction” https://www.youtube.com/watch?v=pH_ibPHK0y0
•
Learn Genetics “Fight or Flight Response” example of Signal Transduction
http://learn.genetics.utah.edu/content/cells/cellcom/
SEE ALSO THE CELL SIGNALING WEBQUEST ACTIVITY FOR ADDITIONAL SPECIFIC
SUPPORT VIDEOS/ANIMATIONS.
Cell Signaling by Single Celled Organisms
• Influences how they respond to the environment
• Examples:
– Quorum sensing in bacteria
• Send and receive signaling relaying info on
population density
• When few organisms present little signaling
• As numbers increase, more signaling, which can result
in different cellular outcomes
© 2011 Pearson Education, Inc.
Cell Signaling by Single Celled Organisms
– Quorum sensing in bacteria
• Pseudomonas aerginosa live in host without harm until
reach a certain population density
• At high density they form a biofilm and cell signaling
changes their gene expression to start producing toxins
– Biofilm: A community of microorganisms attached to
a solid surface; requires the coordinated activity of
numerous bacteria
• Results in host pathology
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Cell Signaling by Single Celled Organisms
– Quorum sensing in Pseudomonas aerginosa
© 2011 Pearson Education, Inc.
Cell Signaling by Single Celled Organisms
– Quorum sensing in bacteria
• Vibrio fischeri is a bioluminescent bacteria that lives in a
mutualistic relationship within the light producing organ of
a Hawaiian squid
• In low numbers and with low signaling, bacteria do not
synthesize the light producing protein
• In high numbers and with high signaling, bacteria do
synthesize the light producing protein
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Cell Signaling by Single Celled Organisms
– Quorum sensing in Vibrio fischeri
© 2011 Pearson Education, Inc.