I think she meantstaff.katyisd.org/sites/thsbiologyapgt/Documents...1 Reception 2 Transduction...
Transcript of I think she meantstaff.katyisd.org/sites/thsbiologyapgt/Documents...1 Reception 2 Transduction...
I think she meant
a different kind of
cellular communication…
Chapter 11
Cellular Communication
Don’t you get it? It’s
not what I said, it’s
what I meant to say!…
External signals are converted to responses within the cell
© 2011 Pearson Education, Inc.
Exchange
of mating
factors
Receptor 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 (pheromones)
Signal Transduction Pathway
series of steps that convert a
signal on a cell’s surface into
a specific cellular response.
a factor
• Pathway similarities
suggest ancestral signaling
molecules evolved in
prokaryotes and later
modified in eukaryotes.
• Quorum Sensing –
Signal molecule
concentration allows bacteria
to sense population density.
© 2011 Pearson Education, Inc.
Figure 11.3
Individual
rod-shaped
cells
Spore-forming
structure
(fruiting body)
Aggregation
in progress
Fruiting bodies
1
2
3
Common trait,
common ancestry…
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 junctions
between animal cells
Plasmodesmata
between plant cells
(a) Cell junctions
(b) Cell-cell recognition
(b) Cell-cell recognition
• 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 Blood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
• Local Signaling messenger molecules that travel only short distances
© 2011 Pearson Education, Inc.
Target cell
Secreting
cell Secretory
vesicle
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling (b) Synaptic signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Neurotransmitter
diffuses across
synapse.
Target cell
is stimulated.
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.
Figure 11.6-1
Plasma membrane
EXTRACELLULAR
FLUID CYTOPLASM
Reception
Receptor
Signaling
molecule
1
Plasma membrane
EXTRACELLULAR
FLUID CYTOPLASM
Reception Transduction
Receptor
Signaling
molecule
Relay molecules in a signal transduction
pathway
2 1
Plasma membrane
EXTRACELLULAR
FLUID CYTOPLASM
Reception Transduction Response
Receptor
Signaling
molecule
Activation
of cellular
response Relay molecules in a signal transduction
pathway
3 2 1
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
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 receptors
–Receptor tyrosine kinases
–Ion channel receptors
© 2011 Pearson Education, Inc.
© 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!
Figure 11.7b
G protein-coupled
receptor
2 1
3 4
Plasma membrane
G protein (inactive)
CYTOPLASM Enzyme
Activated receptor
Signaling molecule
Inactive enzyme
Activated enzyme
Cellular response
GDP GTP
GDP GTP
GTP
P i
GDP
GDP
http://www.youtube.com/watch?
v=4dUJ5GNpfrA&feature=endsc
reen&NR=1
• 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.
Figure 11.7c
Signaling
molecule (ligand)
2 1
3 4
Ligand-binding site
helix in the
membrane
Tyrosines
CYTOPLASM Receptor tyrosine kinase Proteins (inactive monomers)
Signaling
molecule
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 tyrosine
kinase regions
(unphosphorylated
dimer)
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
Activated relay
proteins
Cellular
response 1
Cellular
response 2
Inactive
relay proteins
6 ATP 6 ADP
Figure 11.7d
Signaling molecule (ligand)
2 1 3
Gate closed Ions
Ligand-gated ion channel receptor
Plasma membrane
Gate open
Cellular response
Gate closed
• 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
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
Figure 11.9-1
Hormone (testosterone)
Receptor protein
Plasma membrane
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULAR FLUID
Hormone (testosterone)
Receptor protein
Plasma membrane
Hormone- receptor complex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULAR FLUID
Hormone (testosterone)
Receptor protein
Plasma membrane
Hormone- receptor complex
DNA
NUCLEUS
CYTOPLASM
EXTRACELLULAR FLUID
Hormone (testosterone)
Receptor protein
Plasma membrane
Hormone- receptor complex
DNA
mRNA
NUCLEUS
CYTOPLASM
EXTRACELLULAR FLUID
Hormone (testosterone)
Receptor protein
Plasma membrane
EXTRACELLULAR FLUID
Hormone- receptor complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
I like this Testosterone stuff!
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.
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.
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.
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• 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.
Activated relay molecule
Inactive protein kinase
1 Active
protein kinase
1
Active protein kinase
2
Active protein kinase
3
Inactive protein kinase
2
Inactive protein kinase
3
Inactive protein
Active protein
ATP
ADP
ATP ADP
ATP
ADP
PP
PP
PP
P
P
P i
P i
P i
P
Figure 11.10a Signaling molecule
Cellular response
Small Molecules and Ions as Second Messengers
• “First messenger” - extracellular signal
molecule (ligand) binds to the receptor.
• Second messengers - 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
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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 i P
cAMP
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).
Figure 11.12
G protein
First messenger (signaling molecule such as epinephrine)
G protein-coupled receptor
Adenylyl cyclase
Second messenger
Cellular responses
Protein kinase A
GTP
ATP
cAMP
Calcium Ions and Inositol Triphosphate (IP3)
• Calcium ions (Ca2+) act
as a second messenger in many
pathways
• important second messenger as
cells can regulate its concentration
• Pathways leading to the release of
calcium involve
• inositol triphosphate (IP3) and
diacylglycerol (DAG) as additional
second messengers
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Mitochondrion
EXTRACELLULAR FLUID
Plasma membrane
Ca2 pump
Nucleus
CYTOSOL
Ca2 pump
Ca2 pump
Endoplasmic reticulum (ER)
ATP
ATP
Low [Ca2 ] High [Ca2 ] Key
Figure 11.14-3
G protein
EXTRA- CELLULAR FLUID
Signaling molecule (first messenger)
G protein-coupled receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated calcium channel
Endoplasmic reticulum (ER)
CYTOSOL
Various proteins activated
Cellular responses
Ca2 (second messenger)
Ca2
GTP
Nuclear and Cytoplasmic
Responses
• Signal transduction pathway leads to regulation of cellular activities
• Many signaling pathways regulate the synthesis of enzymes or other proteins 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.
Growth factor
Receptor
Reception
Transduction
CYTOPLASM
Response
Inactive transcription factor
Active transcription factor
DNA
NUCLEUS mRNA
Gene
Phosphorylation cascade
P
Fine-Tuning of the Response
– Amplification of the signal
- Enzyme Cascades
– Specificity of the response
- Different cells, different proteins, different responses
– Overall efficiency of response, enhanced by
scaffolding proteins - Grouping together proteins involved in the same pathway
– Termination of the signal If ligand concentration falls, fewer receptors will be bound.
Unbound receptors revert to an inactive state.
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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• Apoptosis can be triggered by
– An extracellular death-signaling ligand
– DNA damage in the nucleus
– Protein misfolding in the endoplasmic reticulum
• 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 (defective p53
gene) may contribute to some cancers.
© 2011 Pearson Education, Inc.
Interdigital tissue
Cells undergoing apoptosis
Space between digits 1 mm
LECTURE PRESENTATIONS
For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson
© 2011 Pearson Education, Inc.
Lectures by
Erin Barley
Kathleen Fitzpatrick
Ch. 45 Hormones and the
Endocrine System
Overview: The Body’s Long-Distance
Regulators
• Animal hormones are chemical signals that are
secreted into the circulatory system and
communicate regulatory messages within the
body
• Hormones reach all parts of the body, but only
target cells have receptors for that hormone
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© 2011 Pearson Education, Inc.
• Two systems coordinate communication throughout the body:
• The endocrine system secretes hormones that coordinate slower but longer-acting responses including reproduction, development, energy metabolism, growth, and behavior
• The nervous system conveys high-speed electrical signals along neurons; these signals regulate other cells
Hormones bind to target receptors,
triggering specific response pathways
© 2011 Pearson Education, Inc.
Intercellular Communication
• Signals transmitted between animal cells are
classified by two criteria:
– The type of secreting cell
– The route taken by the signal in reaching its target
(a) Endocrine signaling
(b) Paracrine signaling
(c) Autocrine signaling
(d) Synaptic signaling
(e) Neuroendocrine signaling
Figure 45.2a
(a) Endocrine signaling
Blood vessel Response
Response
Response
(b) Paracrine signaling
(c) Autocrine signaling
Hormones secreted by
endocrine cells reach
their targets via the
bloodstream
Local regulators
molecules act over
short distances,
reaching target cells
solely by diffusion
In paracrine signaling,
the target cells lie near
the secreting cells
In autocrine signaling,
the target cell is also
the secreting cell
Figure 45.2b
Synapse
Response
Response
Neuron
Synaptic signaling
Neurosecretory cell
Blood vessel
(e) Neuroendocrine signaling
• Synaptic Signaling - neurons form specialized junctions with
target cells, called synapses
• At synapses, neurons secrete
molecules called neurotransmitters
that diffuse short distances
and bind to receptors on
target cells
• Neuroendocrine Signaling
-specialized neurosecretory
cells secrete molecules
called neurohormones that
travel to target cells via the
bloodstream
Signaling by Pheromones
© 2011 Pearson Education, Inc.
Deer
Wallow
• Molecular communication among members of the same
animal species using pheromones, chemicals that are
released into the environment
• Pheromones serve many functions:
marking trails leading to food,
defining territories
warning of predators
attracting potential mates
Endocrine Tissues and Organs
• Endocrine glands
• Endocrine cells grouped together in ductless
organs that secrete hormones directly into
surrounding fluid
• Exocrine glands
• Glands with ducts that secrete substances onto
body surfaces or into cavities
© 2011 Pearson Education, Inc.
Figure 45.4
Hypothalamus
Pineal gland
Pituitary gland
Thyroid gland
Parathyroid glands (behind thyroid)
Adrenal glands (atop kidneys)
Pancreas
Ovaries (female)
Testes (male)
Organs containing endocrine cells:
Thymus
Heart
Liver
Stomach
Kidneys
Small intestine
Endocrine Tissues
and Organs
Chemical Classes of Hormones
• Three major classes of molecules function as
hormones in vertebrates
Polypeptides (proteins and peptides)
Amines derived from amino acids
Steroid hormones
© 2011 Pearson Education, Inc.
Figure 45.6-2
Lipid- soluble hormone
SECRETORY CELL
Water- soluble hormone
VIA BLOOD
Signal receptor
TARGET CELL
OR
Cytoplasmic response Gene
regulation
(a) (b)
Cytoplasmic response Gene
regulation
Signal receptor
Transport protein
NUCLEUS
Water-soluble
hormones
(hydrophilic)
polypeptides
and
amines
Binds to cell
surface receptor.
Lipid-soluble
hormones
(hydrophobic)
steroid
hormones
pass easily
through cell
membranes Initiates a signal
transduction
pathway leading
to responses in
the cytoplasm,
enzyme
activation, or a
change in gene
expression
Pathway for Lipid-Soluble Hormones
• The response to a lipid-soluble hormone is
usually a change in gene expression
• Steroids, thyroid hormones, and the hormonal
form of vitamin D bind to protein receptors in the
cytoplasm or nucleus
• Protein-receptor complexes then act as
transcription factors in the nucleus
© 2011 Pearson Education, Inc.
• A negative feedback loop inhibits a response by
reducing the initial stimulus, thus preventing
excessive pathway activity
• Positive feedback reinforces a stimulus to
produce an even greater response
• For example, in mammals oxytocin causes the
release of milk, causing greater suckling by
offspring, which stimulates the release of more
oxytocin
© 2011 Pearson Education, Inc.
Feedback Regulation
Pathway Example
Stimulus
Low pH in duodenum
Endocrine cell
S cells of duodenum secrete the hormone secretin ( ).
Hormone
Blood vessel
Target cells of Pancreas
Response Bicarbonate release
Neg
ati
ve f
eed
back
Figure 45.11
• For example, the
release of acidic
contents of the
stomach into the
duodenum stimulates
endocrine cells there
to secrete secretin.
• This causes target
cells in the pancreas,
a gland behind the
stomach, to raise the
pH in the duodenum
by producing
bicarbonate (a base).
Pathway
Example
Stimulus Suckling
Sensory neuron
Po
sit
ive f
eed
back
Hypothalamus/ posterior pituitary
Neurosecretory cell
Neurohormone
Blood vessel
Target cells
Response
Posterior pituitary secretes the neurohormone oxytocin ( ).
Smooth muscle in breasts
Milk release
Figure 45.12
• In a simple
neuroendocrine
pathway, the
stimulus is received
by a sensory
neuron, which
stimulates a
neurosecretory cell
• The neurosecretory
cell secretes a
neurohormone,
which enters the
bloodstream and
travels to target cells
Insulin and Glucagon: Control of Blood Glucose
• Insulin (decreases blood glucose) and glucagon
(increases blood glucose) are antagonistic
hormones that help maintain glucose homeostasis
• The pancreas has clusters of endocrine cells called
pancreatic islets with alpha cells that produce
glucagon and beta cells that produce insulin
© 2011 Pearson Education, Inc.
Figure 45.13a-1
Insulin
Beta cells of
pancreas
release insulin
into the blood.
Homeostasis:
Blood glucose level
(70–110 mg/100 mL)
STIMULUS:
Blood glucose level rises
(for instance, after eating a
carbohydrate-rich meal).
Figure 45.13a-2
Body cells
take up more
glucose.
Insulin
Beta cells of
pancreas
release insulin
into the blood.
Liver takes
up glucose
and stores it
as glycogen. Blood glucose
level declines.
Homeostasis:
Blood glucose level
(70–110 mg/100 mL)
STIMULUS:
Blood glucose level rises
(for instance, after eating a
carbohydrate-rich meal).
Figure 45.13b-1
Homeostasis:
Blood glucose level
(70–110 mg/100 mL)
Glucagon
STIMULUS:
Blood glucose level
falls (for instance, after
skipping a meal).
Alpha cells of pancreas
release glucagon into
the blood.
Figure 45.13b-2
Blood glucose
level rises.
Homeostasis:
Blood glucose level
(70–110 mg/100 mL)
Glucagon signals
Liver to break
down glycogen
and releases
glucose into
the blood.
Alpha cells of pancreas
release glucagon into
the blood. Glucagon
STIMULUS:
Blood glucose level
falls (for instance, after
skipping a meal).
Epinephrine
also, and really
fast…Why?
Body cells take up more glucose.
Insulin
Beta cells of pancreas release insulin into the blood.
Liver takes up glucose and stores it as glycogen.
Blood glucose level declines.
Blood glucose level rises.
Homeostasis: Blood glucose level
(70–110 mg/m100mL)
STIMULUS: Blood glucose level rises
(for instance, after eating a carbohydrate-rich meal).
Liver breaks down glycogen and releases glucose into the blood.
Alpha cells of pancreas release glucagon into the blood.
Glucagon
STIMULUS: Blood glucose level
falls (for instance, after skipping a meal).
Figure 45.13
Target Tissues for Insulin and Glucagon • Insulin reduces blood glucose levels by
– Promoting the cellular uptake of glucose
– Slowing glycogen breakdown in the liver
– Promotes fat storage, not breakdown
– Note: as long as your sugar intake is greater than
sugar requirements, you will always store the excess
as fat.
© 2011 Pearson Education, Inc.
• Glucagon increases blood glucose levels by
– Stimulating conversion of glycogen to glucose in the liver
– Stimulating breakdown of fat and protein into glucose
Diabetes Mellitus
• Diabetes mellitus is perhaps the best-known endocrine
disorder
• Caused by a deficiency of insulin or a (insuling resistance)
in target tissues
• It is marked by elevated blood glucose levels
© 2011 Pearson Education, Inc.
• Type 1 diabetes mellitus (insulin-dependent) is an
autoimmune disorder in which the immune system destroys
pancreatic beta cells
• Type 2 diabetes mellitus (non-insulin-dependent) involves
insulin deficiency or reduced response of target cells due to
change in insulin receptors
Thyroid Regulation: A Hormone Cascade
Pathway
• A hormone can stimulate the release of a series
of other hormones, the last of which activates a
nonendocrine target cell; this is called a hormone
cascade pathway
• The release of thyroid hormone results from a
hormone cascade pathway involving the
hypothalamus, anterior pituitary, and thyroid
gland
• Hormone cascade pathways typically involve
negative feedback
© 2011 Pearson Education, Inc.
Disorders of Thyroid Function and
Regulation
• Hypothyroidism, too little thyroid function, can
produce symptoms such as
– Weight gain, lethargy, cold intolerance
• Hyperthyroidism, excessive production of
thyroid hormone, can lead to
– High temperature, sweating, weight loss,
irritability, and high blood pressure
• Malnutrition can alter thyroid function
© 2011 Pearson Education, Inc.