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Cell Communication per Parrott
Cell communication processes share
common features that reflect a
shared evolutionary history.
a. Communication involves transduction of stimulatory or inhibitory signals from
other cells, organisms or the environment.
b. Correct and appropriate signal transduction processes are generally under strong
selective pressure.
c. In single-celled organisms, signal transduction pathways influence how the cell
responds to its environment.
– • Use of chemical messengers by microbes to communicate with other nearby cells and to
regulate specific pathways in response to population density (quorum sensing)
– • Use of pheromones to trigger reproduction and developmental pathways
– • Response to external signals by bacteria that influences cell movement
d. In multicellular organisms, signal transduction pathways coordinate the activities
within individual cells that support the function of the organism as a whole.
– • Epinephrine stimulation of glycogen breakdown in mammals
– • Temperature determination of sex in some vertebrate organisms
– • DNA repair mechanisms
Local (Short-Distance) Signaling
• Cells may communicate by direct contact
– Plasmodesmata in plant cells
– Gap junctions in animal cells
• allow ions & currents to flow directly from cell to cell -- used in
smooth muscle → synchronized contractions.
• Animal cells can also use cell-cell recognition
– Membrane-bound surface molecules can interact and
communicate
Local (Short-Distance) Signaling
• Messenger molecules can also be secreted by the signaling cell
• Paracrine Signaling:
– One cell secretes (releases) molecules that act on nearby “target” cells
– Example: growth factors
• Juxtacrine Signaling.
– Cell surface proteins from two different cells contact -- used in immune
system. Similar to basic system, but signal molecule is not secreted -remains on cell surface.
• Synaptic Signaling:
– Nerve cells release chemical messengers (neurotransmitters) that stimulate
the target cell
Major types of secreted Signals -- classified by type of cell that makes them
and/or target location.
1. Endocrine:
• Signal molecule secreted by specialized cells in ductless (endocrine) gland
• Gland secretes signal molecule (hormone) into blood.
• Target cell is often far away. Acts long range.
• Examples: Insulin, estrogen, TSH (thyroid stimulating hormone) & TH (thyroid
hormone)
2. Paracrine:
• Usually secreted by ordinary cells
• Target cell is near by -- Receptor is on adjacent cells. Act locally.
o histamines (mediate allergic reactions, responses to inflammation)
o prostaglandins -- initiate uterine cramps; cause fever in response to bacterial infection.
o Many growth factors (like EGF)
3. Autocrine:
• Like paracrine, except receptor is on same cell. ex. = some growth factors
4. Neurocrine:
Chemical Communication
• Neuron secretes signal molecule.
• Signal molecule acts as a neurotransmitter (NT)
• NT acts on receptors on neighbor (gland, another neuron or muscle). Acts
locally, like a paracrine.
• Examples: norephinephrine, acetyl choline.
5. Neuroendocrine:
• Neuron secretes signal molecule, as in previous case.
• Signal molecule acts like a hormone (travels through blood to target).
• Example: Epinephrine (adrenaline).
6. Exocrine:
• Exocrine gland secretions are released by ducts to outside of body (or to inside
of body cavity)*.
• Secretions on outside can carry signals → target in different individual =
pheromones (detected by olfactory receptors in mammals).
Long-Distance Signaling
• Endocrine (hormone)
signaling
– Specialized cells release
hormone molecules, which
travel (usually by diffusion
through cells or through
the circulatory system) to
target cells elsewhere in
the organism
Three Stages of Cell Signaling
There are 3 stages at the “receiving end” of a cellular
conversation:
– In reception, a chemical signal binds to a cellular protein,
typically at the cell’s surface (may also bind
intracellularly).
– In transduction, binding leads to a change in the receptor
that triggers a series of changes along a signaltransduction pathway.
– In response,
the transduced
signal triggers
a specific
cellular
activity.
Stage 1: Reception
• The target cell “detects” that there is a signal molecule
coming from outside the cell
– The signal is detected when it binds to a protein on the cell’s
surface or inside the cell
– The signal molecule “searches out” specific receptor proteins
• The signal molecule is a ligand
– It is a molecule that specifically binds to another one (think enzymes!)
Stage 2: Transduction
• This stage converts the signal into a form that can
bring about a specific cellular response
– One signal-activated receptor activates another protein,
which activates another molecule, etc., etc. (relays)
– These act as relay molecules
– Often the message is transferred using protein kinases,
which transfer phosphate groups from ATP molecules to
proteins
Stage 3: Response
• The signal that was passed
through the signal
transduction pathway
triggers a specific cellular
response
– Examples: enzyme action,
cytoskeleton
rearrangement, activation
of genes, etc., etc.
– Diagram example:
transcription of mRNA
The Specificity of Cell Signaling
• The particular proteins
that a cell possesses
determine which signal
molecules it will respond to
and how it will respond to
them
• Liver cells and heart cells,
for example, do not
respond in the same way to
epinephrine because they
have different collections
of proteins
Signal Transduction
• Reception
• Transduction
• Response
2 Types of Signals
• Lipid-soluble steroids &
thyroid hormones
– Diffuse through plasma mem.
– Enter nucleus
– Form “hormone-receptor
complex”
– H-R complex binds as
transcription factors to
chromosome to activate/
inactivate gene(s)
– i.e. NO
• Peptides & water-soluble
amines
– Hormone (A) binds to
receptor on cell surface
– Activates G- protein
– Activates adenylate cyclase
• Converts ATP to cAMP
– cAMP activates protein
kinases, which produce final
effect.
Types of Receptors
• On Cell Surface -- for water soluble signals. Three major kinds of
cell surface receptors -– G Protein Linked Receptors; Also called G Protein Coupled Receptors or GPCRs.
(TSH & epinephrine use these.)
– Protein Kinase (usually TK) Linked Receptors. These generate
cascades of modifications, but do not always use 2nd messengers.
– Ion Channels. Receptor is part of an ion channel. (Neurons)
• Intracellular -- for lipid soluble signals. All similar, all TF's.
Receptors are transmembrane proteins with an extracellular
binding domain for signal. These are sometimes called
"extracellular receptors" but only ligand binding domain is
extracellular, not the entire protein.
Signal Transduction Pathway Animation
Transduction Pathway Epinephrine
Cell Signaling: Extracellular
• Ligand for Cell Surface Receptor
– (hydrophilic: don’t cross plasma
membrane)
– Ion-Channel-Linked Receptors
• convert chemical to electrical
signals
– G-protein-linked Receptors
• ligand binding  G-Protein
activation by exchange bound GDP
for GTP
• Common structure = 7-pass
membrane protein
– Enzyme-Linked Receptors
Extracellular Signaling Molecules
• Many are Molecular Switches
– switched on by signaling molecule, must also be turned off
• Most common switching mechanisms
(nicotine, morphine & heroin)
– phosphorylation
• signal activated kinase; (kinase = enzyme that phosphorylates a
protein)
• dephosphorylation – phosphatase
– GTP binding proteins:
– GDP bound = inactive,
– GTP bound = active
G-Protein Linked Receptors
• Some activate membrane-bound enzymes => increase “2nd
messengers”
•
– Small and water soluble and easily diffuse
– 2nd messenger = cAMP
adenyl cyclase => ATP to cAMP
cAMP phosphodiesterase => cAMP to ATP
cAMP dependent protein kinase activation by Camp
cAMP => both rapid and slow responses
– 2nd messengers = IP3 & DAG
phospholipase c => IP3 & DAG
IP3 => opens ER Ca+2 channels . >>>> cytoplasmic Ca+2.
> free Ca+2 => many effects
DAG (w free Ca+2) => activated PKC to inner face of membrane
activated PKC => many effects
– 2nd messenger = Ca+2
free Ca+2 => many effect via Ca+2 binding proteins
e.g. calmodulin & calmodulin dependent protein kinases
• The G protein acts as an on-off
switch.
– If GDP is bound, the G protein is inactive.
– If GTP is bound, the G protein is active.
Some regulate ion channels
membrane-bound
increase “2nd messengers”
Some activate
enzymes 
2nd messenger = cAMP
2nd messengers = IP3 & DAG
16_23_slowly_rapidly.jpg
Copyright © 2005 Pearson
Prentice Hall, Inc.
Cell Signaling: Intracellular
Signaling Pathways:
– Same receptor molecule can
interact w/many intracellular
relay systems so same signal &
same receptor  different
effects in different cells
– Same relay system many act on many
different intracellular targets
Signaling Cascade
Critical Functions
• Transduce Signal
• Relay signal from point of
reception to point of
response production
• Amplify signaling molecules
are found in such [low] that
the effect would be minimal
w/o amplification
• Distribute signal to >1
process simultaneously
• Modulate signal to fit other
internal & external
conditions
Cells communicate with each other through
direct contact with other cells or from a
distance via chemical signaling.
a. Cells communicate by cell-to-cell contact.
– • Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells
and killer T-cells.
– • Plasmodesmata between plant cells that allow material to be transported from cell to cell.
b. Cells communicate over short distances by using local regulators that target cells
in the vicinity of the emitting cell.
–
–
–
–
• Neurotransmitters
• Plant immune response
• Quorum sensing in bacteria
• Morphogens in embryonic development
c. Signals released by one cell type can travel long distances to target cells of
another cell type.
– 1. Endocrine signals are produced by endocrine cells that release signaling molecules, which
are specific and can travel long distances through the blood to reach all parts of the body.
•
•
•
•
•
Insulin
Human growth hormone
Thyroid hormones
Testosterone
Estrogen
•
SIGNALING
PATHWAYS CAN BE
HIGHLY
INTERCONNECTED
F16-38
•
(like nerve networks in brain or
microprocessors in a computer)
•
“... a major challenge
to figure out how
cell communication
pieces fit together
to allow cells to
integrate
environmental
signals and to
respond
appropriately”
Cell Signaling
Death Signaling, 2, 3
Cell Signaling in Plants
Signaling Between Plants & Pathogens
Phytochrome signaling
Resources
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Pathophysiology of the Endocrine System
Signal Transduction Pathways
Cell-Cell Adhesion in Leukocyte Extravasation
Fight or Flight Response
Fibroblast Cell Signals
Fight or Flight 2
Cell Signaling Links
Bozeman Signal Transduction Pathways
Signal Transduction by Extracellular Receptors Tutorial
Cell Signaling Flash Movies
p53 Song
Apoptosis Animation
Essential knowledge 3.D.1: Cell communication processes share common features that reflect a shared evolutionary history.
•
a. Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment. [See also 1.B.1]
•
b. Correct and appropriate signal transduction processes are generally under strong selective pressure.
•
c. In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.
•
• chemical messengers by microbes to communicate with nearby cells and regulate specific pathways in response to population density (quorum sensing),
pheromones to trigger reproduction & developmental pathways, Response to external signals by bacteria that influences cell movement
•
d. In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a
whole.
•
LO 3.31 The student is able to describe basic chemical processes for cell communication shared across evolutionary lines of descent. [See SP 7.2]
•
LO 3.32 The student is able to generate scientific questions involving cell communication as it relates to the process of evolution. [See SP 3.1]
•
LO 3.33 The student is able to use representation(s) and appropriate models to describe features of a cell signaling pathway. [See SP 1.4]
Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.
•
a. Cells communicate by cell-to-cell contact.
•
• Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells. [See also 2.D.4]
•
• Plasmodesmata between plant cells that allow material to be transported from cell to cell.
•
b. Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell.
•
• Neurotransmitters
• Plant immune response
• Quorum sensing in bacteria • Morphogens in embryonic development
Essential knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response.
•
a. Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein.
•
1. Different receptors recognize different chemical messengers, which can be peptides, small chemicals or proteins, in a specific one-to-one relationship.
•
2. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal.
•
• G-protein linked receptors
• Ligand-gated ion channels
• Receptor tyrosine kinases
•
b. Signal transduction is the process by which a signal is converted to a cellular response.
•
1. Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the
cell.
•
2. Second messengers are often essential to the function of the cascade.
•
• Ligand-gated ion channels
• Second messengers, such as cyclic GMP, cyclic AMP calcium ions (Ca2+), and inositol
triphosphate (IP3)
•
3. Many signal transduction pathways include:
•
i. Protein modifications (an illustrative example could be how methylation changes the signaling process)
•
ii. Phosphorylation cascades in which a series of protein kinases add a phosphate group to the next protein in the cascade sequence
•
LO 3.36 The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted to a
cellular response.
Essential knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response.
•
a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic.
•
• Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera
•
• Effects of neurotoxins, poisons, pesticides
•
• Drugs (Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs)