Transcript Ch 11 Cell Communication

Cell Communication
Chapter 11
Overview: Cellular Messaging
• Cell-to-cell communication essential for
multicellular & unicellular organisms
• Cells communicate with each other via
chemical signals
• “fight-or-flight response” triggered by
signaling molecule (hormone) epinephrine
How does cell signaling trigger the desperate flight of this gazelle?
Signal Transduction Pathways
• convert signal from one
form to another in cell
• verbal instruction 
written text  email 
voice mail  action
• response due to original
signal at cell’s surface
Chemical Signals in Cells
• Hydrophilic: can’t pass through the cell
membrane; binds to receptor protein (integral)
within cell membrane.
•
•
•
•
Proteins
Amino acids
Peptides
Nucleotides
Chemical Signals in Cells
• Hydrophobic: pass
through cell
membrane; act on
receptor proteins in
cytoplasm or nuclear
membrane
• steroid hormones
• gasses
Types of Cell Communication
Signal cell  Target cell
• Direct contact
• Cell to cell recognition
• Cell Junctions
• Local Regulation
• Distance Regulation
Direct: Cell to Cell Recognition
• glycoproteins, glycolipids,
or other molecules on cell
membrane are recognition
markers
• important in immune
response, embryonic
development
Cell-cell recognition. Two cells in an animal may communicate
by interaction between molecules protruding from their surfaces.
Direct: Cell Junctions
• communication between cytoplasm of neighboring cells
• ions in cytoplasm, electrical signals can pass through
• Gap Junctions: animal cells
• Plasmodesmata: plant cells
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
Cell junctions. Both animals and plants have cell junctions that
allow molecules to pass readily between adjacent cells without
crossing plasma membranes.
Local Regulators
Communicate & influence cells in close proximity
• does not travel through the blood stream
• Paracrine: simultaneous response by more than one cell
• growth factors: cause multiplication and growth of target cells
• Synaptic: nervous system, at synapses
• neurotransmitters diffuse from one nerve cell to stimulate the next
Long Distance Regulators
Long-distance signaling
• Endocrine signaling
Endocrine cell
Blood
vessel
• Hormones
• carried in animal’s bloodstream
• endocrine cells secrete hormones
 circulatory system  target cells
respond
• carried in sap of plants, or diffuse
in air as gas
• Ethylene gas
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal
signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Cell Signaling
EXTRACELLULAR
FLUID
Reception
CYTOPLASM
Plasma membrane
Transduction
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
1. Reception: detection of message (signal) by a receptor protein
2. Transduction: receptor changes shape and initiates a cascade
of events
3. Response: activation of cellular response in the target cell
Video: cell signaling overview
Reception
Receptors: proteins specific to
signaling molecules (ligands)
• Intracellular Receptors: within
cytoplasm or nucleus
• steroid or hormone receptors:
hydrophobic
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
• Plasma Membrane Receptors:
proteins in the cell membrane
• Hydrophilic receptors for protein
hormones
DNA
mRNA
NUCLEUS
What type of receptor is shown here?
CYTOPLASM
New protein
Plasma Membrane Receptors
• Used for hydrophilic ligands that can’t diffuse into
the cell through the cell membrane
• G-protein-linked receptor
• Receptor tyrosine kinase
• Ligand-gated ion channel
G-Protein-Linked Receptor
GPCRs
• Signal molecule (ligand)
attaches to receptor which
changes shape
• G-protein binds to receptor
& is activated by the
conversion of GTP to GDP
• phosphorylated
• G-protein activates an
enzyme which triggers a
cascade in the cell to the
target
– Used for vision, smell, taste
– 60% of medicines activate Gproteins
How does G-protein act
as an off/on switch?
Signal-binding site
See page 206
Segment that
interacts with
G proteins
G-protein-linked
Receptor
Plasma Membrane
Activated
Receptor
Inctivate
enzyme
Signal molecule
GDP
CYTOPLASM
G-protein
(inactive)
Enzyme
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
Receptor Tyrosine Kinase
• Signal molecules bind to receptors activating 2 kinases
at a time
dimer
• ATP further activates the dimers
• Activated relay proteins trigger cascades within cell
leading to a cellular response.
• Used to trigger multiple reactions
at once
• Cell growth & reproduction
• Abnormal tyrosine kinases are
thought to cause some cancer
• Herceptin and HER2
What are 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
Ligand-Gated Ion Channels
• Signal molecule (ligand)
opens gate for specific ions
• Once ions enter specific
reactions take place
– Na+ action potential in nerve
cells
– Ca+ muscle contraction
Signal
molecule
(ligand)
Gate closed
Ligand-gated
ion channel receptor
Ions
Plasma
Membrane
Gate open
Cellular
response
Gate close
Transduction
• Cascade
• Step 1 step 2  step 3
 step 4  reaction
• Activated by
phosphorylation
– ATP  ADP + P
– Protein Kinases
• Deactivated by
dephosphorylation
– P removed
– Protein phosphatases
Signal transduction video
Signaling molecule
Receptor
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
Second Messengers
• Small, non-protein, water
soluble, ions
• Cyclic AMP
• Calcium Ions Ca2+
• Receptors on the outside
of the membrane are the
1st messengers
Cyclic AMP
• Epinepherine
glycogen breakdown
• Epi binds to membrane receptor,
– Adenylyl cyclase enzyme in membrane converts ATP to
cAMP
– many cAMP can be formed within seconds
• Used with G proteins
NH2
N
N
O
O
O
N
N
–
O P O P O P O Ch2
O
O
O
N
N
O
Pyrophosphate
P Pi
O
CH2
Phosophodiesterase
O
OH
Cyclic AMP
What does phosphodiesterase do?
N
N
O
HO P O CH2
O
O
P
O
N
N
N
N
Adenylyl cyclase
O
OH OH
ATP
NH2
NH2
O
H2O
OH OH
AMP
First messenger
(signaling molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Explain the mechanism of
disease in cholera
Second
messenger
Protein
kinase A
Cellular responses
2+
Ca
• Most widely used 2nd messenger
• Increase in Ca2+  muscle contraction and cell division
– Actin contraction by
microfilaments
• Greening of plants in
response to sunlight
• Used with all 3
membrane receptors
– G-protein
– Tyrosine Kinase
– Ligand Gated Ion
Channel
EXTRACELLULAR
FLUID
ATP
Plasma
membrane
Ca2+
pump
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
ATP
Ca2+
Endoplasmic
reticulum (ER)
pump
Key
High [Ca2+]
Low [Ca2+]
• 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
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
Ca2
(second
messenger)
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
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
Response
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
• Signals can be amplified
as they are sent from
messenger to messenger.
• Signals are specific to
target cells and enzymes
• Not all cells respond to a
signal even though the
signal will be sent to all
cells in the blood
specificity
Nuclear and Cytoplasmic Responses
• Signal transduction pathways lead to regulation of one
or more cellular activities
• Nucleus
– regulates protein synthesis by turning genes on or off
– final activated molecule in the pathway functions as a
transcription factor
• Cytoplasm
– Other pathways regulate the activity of the enzymes
Growth factor
Nuclear Response
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Cytoplasmic Response
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Glycogen
Glucose 1-phosphate
(108 molecules)
Apoptotic Pathways and the Signals
That Trigger Them
• Caspases: main proteases (enzymes that cut up
proteins) that carry out apoptosis
• Apoptosis can be triggered by
– Extracellular death-signaling ligand
– DNA damage in the nucleus
– Protein misfolding in the endoplasmic reticulum
Interdigital tissue
Cells undergoing
apoptosis
Space between
digits
1 mm
• Effect of apoptosis during paw development
in the mouse.
• Apoptosis eliminates cells in the interdigital
regions, forming the digits.