Transcript Chapter 11 (Nov 30

Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
- Paracrine – local signaling from 1 cell to another in close range
- Endocrine – long-distance signaling involving hormones
Local signaling
Long-distance signaling
Target cell
Secreting
cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(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.
Endocrine cell
Target cell
is stimulated
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Figure 11.3 Communication by direct contact between cells
Plasma membranes
Gap junctions
between animal cells
Plasmodesmata
between plant cells
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
(b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
EXTRACELLULAR
FLUID
1 Reception
Receptor
Signal
molecule
CYTOPLASM
Plasma membrane
2 Transduction
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction pathway
Signal
molecule
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
- Response – cell’s response to the signal
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors
- G-protein-linked receptors
-membrane-bound (integral proteins)
- Tyrosine kinase receptors
- Ligand-gated ion channels
Fig. 11.6 Steroid hormone interacting with an intracellular receptor
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
hormone testosterone
passes through the
plasma membrane.
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
3 The hormonereceptor complex
enters the nucleus
and binds to specific
genes.
DNA
mRNA
NUCLEUS
1 The non-polar steroid
4 The bound protein
stimulates the
transcription of
the gene into mRNA.
New protein
5 The mRNA is
translated into a
specific protein.
CYTOPLASM
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors
- G-protein-linked receptors
- Associated with a cytoplasmic G-protein
- G-protein binds either GDP (inactive) or GTP (active)
- Ligand binding
- Causes a change in receptor shape which
- Attracts the inactive G-protein
- GTP displaces GDP activating the G-protein
- Activated G-protein can then activate other specific molecules
Figure 11.7 Exploring Membrane Receptors
Signal-binding site
G-PROTEIN-LINKED RECEPTORS
Segment that
interacts with
G proteins
G-protein-linked
receptor
Plasma Membrane
Activated
receptor
Signal molecule
GDP
CYTOPLASM
G-protein
(inactive)
Enzyme
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
Cellular response
Inactive
enzyme
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors
- G-protein-linked receptors
- Tyrosine kinase receptors
- Kinase – enzyme that phosphorylates
- Ligand binding
- Causes receptor to form a dimer
- Cytoplasmic tails phosphorylate each other because…
- ATP is hydrolyzed & terminal phosphate is added to tyrosine aa
- Activated receptors can then activate specific relay proteins
RECEPTOR TYROSINE KINASES
Signal-binding site
Signal
molecule
Signal
molecule
 Helix in the
Membrane
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Dimer
Activated
relay proteins
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
Tyr
Tyr
P Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
Tyr P
Tyr P
P Tyr
Tyr P
P Tyr
Tyr P
Tyr P
P Tyr
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors
- G-protein-linked receptors
- Tyrosine kinase receptors
- Ligand-gated ion channels
- Ligand binding
- Causes a change in shape
- Allows specific ions to move down concentration gradient
- e.g. neurotransmitters between neurons
Signal
molecule
(ligand)
Gate
Gate
close
Closed
Ions
Ligand-gated
ion channel receptor
Plasma
Membrane
Gate open
Cellular
response
Gate close
ION CHANNEL RECEPTORS
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction pathway
Signal
molecule
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
- Often done by protein phosphorylations
- Protein kinases phosphorylate other relay molecules (kinases)
- Inactivated by phosphatases
Figure 11.8 A phosphorylation cascade
(involves several protein kinases)
Signal molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
1 A relay molecule
activates protein kinase 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
1
Inactive
protein kinase
2
ATP
ADP
Pi
PP
Inactive
protein kinase
3
5 Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse.
3 Active protein kinase 2
then catalyzes the phosphorylation (and activation) of
protein kinase 3.
P
Active
protein
kinase
2
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
4 Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
- Often done by protein phosphorylations
- 2nd messengers
- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP
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
Phoshodiesterase
O
OH
Cyclic AMP
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
Fig 11.10 cAMP as a second messenger in a G-protein-signaling
pathway
First messenger
(signal molecule
such as epinephrine)
G protein
G-protein-linked
receptor
Adenylyl
cyclase
GTP
ATP
Second
cAMP messenger
Protein
kinase A
Cellular responses
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
- Often done by protein phosphorylations
- 2nd messengers
- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP
- Ca+2 ions
- Released from ER
Figure 11.11 Maintenance of calcium ion concentrations in an
animal cell
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2+
pump
ATP
Mitochondrion
Nucleus
CYTOSOL
Ca2+
pump
ATP
Ca2+
Endoplasmic
reticulum (ER)
pump
Key
High [Ca2+]
Low [Ca2+]
Figure 11.12 Calcium and IP3 in signaling pathways
How does Ca+2 get released from the ER?
- more 2nd messengers
- IP3
- follow the numbers
1 A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
2 Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
3 DAG functions as
a second messenger
in other pathways.
Signal molecule
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
Phospholipase C
PIP2
IP3
(second messenger)
Figure 11.12 Calcium and IP3 in signaling pathways
1 A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
2 Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
3 DAG functions as
a second messenger
In other pathways.
Signal molecule
(first messenger)
G protein
DAG
GTP
PIP2
G-protein-linked
receptor
Phospholipase C
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
Ca2+
(second
messenger)
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
5 Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
IP3
(second messenger)
Figure 11.12 Calcium and IP3 in signaling pathways
1
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRACELLULAR
FLUID
2 Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
3 DAG functions as
a second messenger
in other pathways.
Signal molecule
(first messenger)
G protein
DAG
GTP
PIP2
G-protein-linked
receptor
Phospholipase C
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Various
proteins
activated
Ca2+
CYTOSOL
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
Cellular
responses
Ca2+
(second
messenger)
5 Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
6 The calcium ions
activate the next
protein in one or more
signaling pathways.
Chapter 11: Cell Communication
1. What is the difference between paracrine signaling & endocrine signaling?
2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
- Transduction – conversion of the received signal to a specific
cellular response
- Often done by protein phosphorylations
- Protein kinases phosphorylate other relay molecules (kinases)
- Inactivated by phosphatases
- 2nd messengers
- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP
- Ca+2 ions
- IP3 - inositol triphosphate
- Response – cell’s response to the signal
3. What is meant by signal amplification?
- A single ligand can activate millions of molecules during a cell’s response
Figure 11.13 Cytoplasmic response to a signal: the stimulation of
glycogen breakdown by epinephrine
Reception
- Cytoplasmic signal
amplification
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
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)
Figure 11.14 Nuclear responses to a signal: the activation of a
specific gene by a growth factor
Growth factor
- Nuclear signal
amplification
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Chapter 11: Cell Communication
1.
2.
3.
4.
What is the difference between paracrine signaling & endocrine signaling?
What are the 3 stages of cell signaling?
What is meant my signal amplification?
How can cells have different responses to the same signal?
Signal
- Different relay proteins
molecule
- Cross-talk w/ diff. signals
- Different receptor types Receptor
Relay
molecules
Response 1
Response 2 Response 3
Cell A. Pathway leads
to a single response
Cell B. Pathway branches,
leading to two responses
Activation
or inhibition
Response 4
Cell C. Cross-talk occurs
between two pathways
Response 5
Cell D. Different receptor
leads to a different response
Chapter 11: Cell Communication
1.
2.
3.
4.
5.
What is the difference between paracrine signaling & endocrine signaling?
What are the 3 stages of cell signaling?
What is meant my signal amplification?
How can cells have different responses to the same signal?
How do scaffolding proteins help cell communication?
- By binding several different molecules together for quicker process
Signal
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Three
different
protein
kinases