Cellular Communication
Everything an animal does involves
communication among cells, Cell signaling refers
to the communication between cells
– A Signaling cell sends a signal
– A Target cell: receives the signal
• The big questions; how far does the signal
need to travel, how fast does it need to
travel, how will it enter the cell & be
received, and does it need amplification?
Types of Signaling
1. Physical contact, Gap junctures directly connect the
cytoplasms of two cells, via a water-filled channel
permeable to small second messengers such as Ca2+
or cAMP but not macromolecules
2. Endocrine: broadcasted over the entire organism,
secreting the signal (hormone) into the bloodstream of
an animal or the sap of a plant.
3. Paracrine secreted locally, remaining in the
neighborhood of the secreting cell.
4. Neuronal: A neuron sends electrical signals along its
axon, stimulating the release of signals called
neurotransmitters, which will be received by the target
cell.
Gap Junctures: Direct Signaling
•
Gap junctions –
specialized protein
complexes create an
aqueous pore between two
adjacent cells
Hydrophilic chemical
messengers can travel
through the lipid
membrane
•
–
Typically involves the
movement of ions
Figure 4.2
Local
Signaling
Cells release a chemical that binds
to a receptor on the target cell
.
(in
autocrine
signals, - the
signal acts on) the
cell itself
Paracrine -
LOCAL
chemical signals interact with
receptors on nearby cells.
Distance Signals
Endocrine: 
hormone is
transported by the
circulatory system
 Neural: electrical
signal travels along a
neuron and releases a
neurotransmitter
To Review
1. Kinds of signals. Who is local, who is
distance?
a) Direct – hydrophilic small compounds
that travel through channels in gap
junctures
b) Paracrine (and autocrine)
c) Endocrine
d) Neural: combination of electrical and
chemical
Indirect Signaling
Three steps
1. Release of chemical messenger from the
signaling cell (large or small)
2. Transport of the messenger through the
extracellular environment to the target
cell (local or distant)
3. Communication of the signal to the target
cell (membrane receptor or intracellular
receptor)
Thee Kinds of Hormones
• Many substances act as chemical
signals – not all are “hormones”
• Hormones are defined as chemical
substances produced by endocrine glands
and secreted in the circulatory system.
• Three categories:
– Peptides: , charged chains of
2 to 200 amino acids
– Amines: small molecules
derived from amino acids
– Steroids: several carbon
rings, derived from cholesterol
non polar
•
Release & of the Chemical
Messenger
Hydrophilic
messengers are
packed into
vesicles where they
are stored until
they are released
by exocytosis
•
– Exocytosis –
vesicle fuses with
the plasma
membrane and
releases its
contents
These messengers
dissolve in aqueous
solutions like
extracellular fluid and
blood, bind to surface
receptor, and this
triggers a change in
enzyme activities
inside the cell
Hydrophobic
messengers
can cross the
cell membrane
by diffusion
•Hydrophobic
messengers bind to
carrier proteins in
the blood They then
can bind to
receptors on the
surface – or inside
the cell
At the Target Cell
• Hydrophilic (peptide
and amine)
messengers bind to
surface receptor, and
this triggers a change
in enzyme activities
inside the cell
• Hydrophobic
messengers bind to
carrier proteins in the
blood, and may bind to
receptors on the
surface – or inside the
cell
Transport to the Target Cell
• Hydrophilic (peptide and
amine) messengers
dissolve in aqueous
solutions like extracellular
fluid and blood, bind to
surface receptor, and this
triggers a change in enzyme
activities inside the cell
Hydrophobic
messengers
bind to carrier
proteins in the
blood They
then can bind to
receptors on
the surface – or
inside the cell
Intracellular Receptors
• Regulate the
transcription of
target genes
by binding to
specific DNA
sequence and
increasing or
decreasing
mRNA
production
Figure 4.11
Chemical Messengers
• Two main types
Table 4.1
Ligand-Receptor Interactions
• Only the correctly
shaped ligand (natural
ligand) can bind to the
receptor
• Ligand mimics (e.g.,
drugs and poisons)
– Agonists – activate
receptors
– Antagonists – block
receptors
Figure 4.6
Ligand-Receptor Dynamics
• L + R  L-R  response
• More free ligand (L) or receptors (R) will
increase the response
• Receptors can become saturated
Figure 4.7
Signal Transduction Pathways
1.
2.
Convert signals from one
form to another
Four components
a.
b.
c.
d.
Receiver: ligand binding
receptor
Transducer:
conformational change of
the receptor
Amplifier: the signal
transduction pathway
increases the number of
molecules affected
Responder: something
that responds to the signal
Figure 4.9
Types of Receptors
Figure 4.10
Ligand-Gated Ion Channels
•
•
•
•
Ligand binds to receptor
Receptor changes shape opening a channel
Ions move across the membrane
Concentration and electrical gradients dictate the direction
of ion movement
• Movement of ions change ion concentrations which alters
the membrane potential
Figure 4.13
Receptor Enzymes
• When activated by a ligand the catalytic
domain starts a phosphorylation cascade
• Named based on the reaction catalyzed
Figure 4.14
G-Protein-Coupled Receptors
•
•
•
Transmembrane protein that interacts with intracellular G-proteins
G-proteins – named for their ability to bind guanosine nucleotides
Activate second messengers
Figure 4.19
Second Messengers
Table 4.2
Nervous System
• Specialized collection of cells that can
carry signals across long distances
• Neurons allow electrical signals to be
propagated across long distances within a
single cell
• Synapse – region in between two neurons
or a neuron and other target cells
– Gap junctions
– Chemical: neurotransmitters
Endocrine System
• Sends chemicals (hormones) through the blood
• Produced by endocrine glands
• Other chemicals can act as hormones, e.g.,
neurohormones
• Non-endocrine organs can produce hormones,
e.g., heart
• Three types of hormones
– Peptides
– Steroids
– Amines
Three Types of Hormones
Table 4.4
To review: Peptide Hormones
•
•
•
•
Synthesized on the rough ER
Stored in vesicles
Leave signaling cell via exocytosis
Soluble in aqueous solutions and travel to
the target cell dissolved in the extracellular
fluid
• Hydrophilic: cannot cross the target cell
membrane
• Bind to transmembrane receptors
• Rapid effects on the target cell
Synthesis of Peptide Hormones
Peptides are charged & hydrophilic –
note the storage in vesicles
Figure 4.23
Steroid Hormones
• Derived from cholesterol
• Hydrophobic: can pass through the plasma
membrane
• Enzymes for synthesis are in the smooth ER or
mitochondria
• Cannot be stored within the cell
• Must be synthesized on demand
• Transported to target cell by carrier proteins
– Slow effects on the target cell (regulate transcription)
– exception: stress hormone cortisol has rapid nongenomic effects
Three Classes of Steroid Hormones
• Mineralocorticoids
– Electrolyte balance
– e.g., aldosterone
• Glucocorticoids
– Stress hormones
– e.g., cortisol
• Reproductive hormones
– Regulate sex-specific characteristics and
reproduction
– e.g., estrogen, progesterone, testosterone
Amine Hormones
• Chemicals that possess amine (-NH2)
• e.g., acetylcholine, catecholamines
(dopamine, norepinephrine, epinephrine),
serotonin, melatonin, histamine, thyroid
hormones
• Some are true hormones, some are
neurotransmitters, some are both
• Diverse effects
Exocrine Cell Signaling
• Secretions via ducts to the outside of the body
including the skin, respiratory surfaces, and the gut
• e.g., salivary glands, prostate, sweat glands
• Cell-to-cell: pheromones, allelochemicals
Figure 4.28
Regulation of Cell Signaling
• Feedback
– Positive – output acts as a further stimulus
– Negative – output reduces the stimulus
• Vary in complexity
• Direct feedback : endocrine gland responds to a
stimulus, releasing a hormone to the circulatory
system. The hormone reaches a target organ,
binds to a receptor, and causes a response that
shuts down the endocrine release (negative
feedback
Regulation of Cell Signaling,.
Figure 4.29
First order: Parathyroid hormone
regulation of calcium ions
• When calcium level is low
– parathyroid hormone is
released,
• The hormone travels to
the blood, binds to Gprotien receptors, and
causes release of calcium
ions to the blood
• This “turns off” the release
of parathyroic hormone.
Direct Endocrine
Pathways
1.
2.
3.
4.
Endocrine organ acts as the
receptor, the integrating
center, and the endocrine
organ
When calcium level is low –
parathyroid hormone is
released
The hormone travels to the
blood, causes release of
calcium ions to the blood
The release of the hormone
is the negative feedback the
shuts down the system
Figure 4.30
Second Order Endocrine
Pathways
• e.g., Epinephrine – “fight-orflight” response
• Sense organ perceives and
alarming stimulus
• Sensory nerves send signals to
the brain
• Brain integrates the signals and
sends signal out via the motor
nerves
• Adrenal medulla responds to
this signal by releasing
epinephrine
• Epinephrine interacts with the
heart and muscles
Second order: Epinephrine
• Sensory nerves send
signals to the brain (“I
see a predator”)
Brain sends signals to
many parts of the body
including the adrenal
medulla)
• Epinephrine released
from adrenal medulla
interacts with many
organs
There is a stage between
the initial stimulus, and the
release of the hormone
Third order: Anterior Pituitary
Hypothalamus synthesizes and secretes a neurohormone, into the
blood, this enters the portal system to the anterior pituitary, causing
the release of thyroid stimulating hormone that travels to target
organs
1. The hypothalmus
releases a Tropic
hormones – cause
the release of
another hormone
Figure 4.33
Simultaneous Response
Pathways
• Insulin is part of a
direct stimulusresponse pathway
and a secondorder pathway
Figure 4.31
Pituitary Hormones
• The pituitary gland secretes many
hormones
• Two distinct sections
– Anterior pituitary (example of third order)
– Posterior pituitary (example of first order)
• Regulated at many levels
Posterior Pituitary
• Extension of the
hypothalamus
• Neurons that
originate in the
hypothalamus
terminate in the
posterior pituitary
• Cell bodies
synthesize
neurohormones that
travel in vesicles
down the axons
• e.g., Oxytocin and
vasopressin
• First-order endocrine
pathway
Figure 4.32
Regulation of Blood Glucose
• Very tightly
controlled
– Too low  brain
cannot function
– Too high  osmotic
balance of the blood
is disturbed
• Hormones: insulin
and glucagon
• Antagonistic pairing
– hormones have
opposite effects
Figure 4.36
Evolution of Cell Signaling
• Mechanisms for cell signaling share many
similarities in all animal groups
• Must have originated in a common
ancestor
Unicellular Organisms
• Can sense and respond to their environment
• Use mechanisms similar to cell signaling in animals
• Examples
– Motile bacteria: sense and move towards chemoattractants
using transmembrane receptor proteins
– Yeast: secrete mating factor pheromones that bind only to
receptors on cells of the opposite mating type
– Slime molds: free-living amoeboid organisms that form
multicellular colonies; secrete cAMP to attract other cells
that have specific receptors for cAMP
Plants vs. Animals
• Pathways have similar outlines, but
different details
• Similarities
– Use Ca2+ as a secondary messenger
– Have many pathways that involve protein
kinases
• Differences
– Plants do not have receptor tyrosine kinases
or Ras proteins
– Plants have unique transmembrane
serine/threonine kinases
Vertebrates vs. Invertebrates
•
•
•
All have nervous systems; except sponges
Circulatory systems arose independently
in several groups, e.g., arthropods and
vertebrates
Endocrine systems could only arise in
groups with circulatory systems and
therefore also arose independently
Vertebrate vs. Invertebrate
Hormones
• All vertebrates use a series of steroid
hormones, e.g., estrogens, androgens, and
corticosteroids
• Only estrogen has been found in
invertebrates
• Insects and crustaceans use a different series
of steroids (e.g., ecdysone) to regulate
molting and metamorphosis
Vert. vs. Invert. Endocrine
Systems
• Correlation between the complexity of the
endocrine system and the complexity of the
body form
• Invertebrates vs. vertebrates
– Fewer endocrine glands and most endocrine
signaling uses neurohormones
– More first-order endocrine loops
– Fewer third-order endocrine loops
Vertebrate Hormones
• Alterations in the way tissues respond to a
hormone, rather than a change in the hormones
• Similarities
– Many hormones are affective across many groups, e.g.,
human growth hormone increase growth rate in fish,
estrogen from pregnant mares are used in menopausal
women
• Differences
– Prolactin stimulates milk production in mammals, inhibits
metamorphosis and promotes growth in amphibians, and
regulates water balance in fish