BIO 110 – CELL COMMUNICATION  Yeast A produces secretion (A factor) which has
complementary receptor in alpha yeast.
Cell Communication
 External signals are converted to response within the cell
 Some proteins are receptors. They receive chemicals
which function as signals.
 External signals are converted to responses in the cell
(how cells and organisms communicate)
 Signals can be light and touch but are most often
chemicals
 Three components:
 Reception
 Transduction
 Response of cell
 Apoptosis integrates multiple cell-signaling pathways
 Essential for multicellular and unicellular organisms
 They communicate with each other via chemical signals
Example:
Predator-prey relationship
 Fight or flight response – either you fight back or run away
from the situation
 In this kind of situation, the hormone
adrenaline/epinephrine (signaling molecule) is secreted
from adrenal glands. It stimulates the cells to secrete
glucose. If there is an abundance of glucose, mitochondria
can convert it into ATP. (You have a lot of energy)
Thigmonasty/Seismonasty
 Mimosa pudica – has receptors sensitive to touch that
cause change in pressure in cells (folding of leaves)
Exchange of mating factors in yeast – Saccharomyces
cerevisiae (used to make bread, wine and bear)
1. Exchange of mating factors
 Alpha yeast produces alpha factor which has
corresponding receptor in A yeast
2. Mating
 Because of the binding of the substances with the
receptors, it will result to binding, conformational
changes in the membrane and the fusion of the two
membranes
3. New a/alpha cell
 After fusion, there will be exchange of nuclear
materials.
 Result: Hybrid organism/organism with the two
genetic information (reproduction by chemical
signaling)
 The unique match between mating factor and receptor is
key to ensuring mating only among cells of the same
species of yeast.
 Researchers were able to genetically engineer yeast cells
with both receptors and mating factors altered so that the
altered proteins would bind to each other but not to the
original proteins of the parent cells. (no mating with parent
cell)
 Cellular response of mating happens in steps called signal
transduction pathway
 Pathway similarities suggest that ancestral signaling
molecules evolved in prokaryotes and were modified later
in eukaryotes
Communication among prokaryotes
1. Individual rod-shaped cells
 The concentration of signaling molecules allows
bacteria to sense local population density
 They can attract their own species through secretions
2. Aggregation in progress
 They exchange genetic information
3. Spore-forming structure (fruiting body)
 Hybrid bacteria – reproductive bodies
Quorum Sensing (QS) – allows bacterial populations to
coordinate their behaviors in activities that require a given
number of cells acting synchronously
 A bacterial cell-cell communication process that involves
the production, detection and response to extracellular
signaling molecules called autoinducers (secreted by
bacteria)
 Bacterial cells secrete molecules that can be detected by
other bacterial cells
 Sensing of signaling molecules allow bacteria to monitor
own local density
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 Autoinducers accumulate in the environment as the
bacterial population density increases and bacteria
monitor this information to track changes in their cell
numbers and collectively alter gene expression
 Helps bacteria anchor into their substrate (they exist in
colonies)
 Allow bacterial population to coordinate their behaviors so
that they can carry out activities that are only productive
when performed by a given no. of cells in synchrony
 Formation of biofilm – aggregation of bacteria adhered to
a surface; the cells in the biofilm derive nutrition from the
surface they are on.
Example: slimy coating on fallen leaves, slimy coating on
teeth (tartar – consist of bacteria and secretory materials
secreted by bacteria (dumadami nang dumadami), they
take nourishment from teeth and result in cavities
 Secretion of toxins by infectious bacteria – interfering
signaling pathway as alternative treatment
Local Signaling
A. Communication by direct contact between cells
1. Cell Junction – directly connect cytoplasm of adjacent
cells
 When two cells are adjacent, there is formation of
channels that allow transport of ions (gap junctions,
intercalated discs in cardiac muscle cells,
plasmodesmata)
 Signaling substances dissolved in cytosol can pass
freely between neighboring cells.
2. Cell-cell recognition – direct contact between
membrane-bound cell-surface molecules
 Presence of glycoproteins in cell membrane that have
receptors on the adjacent cell
 Binding of glycoprotein and receptor of adjacent cell
would exert an effect on neighbouring cell
 Important in embryonic development and immune
response
B. Cell signalling by secreted molecules
1. Paracrine signalling – signaling molecules are
secreted by signaling cell and travel short distance
 One cell (through the vesicles) would secrete
materials into the extracellular matrix
 The materials secreted will affect the nearby cell
of the same organ.
 Local regulators influence cells in the vicinity
 Specific receptors for signal are within the same
locality (organ)
 Examples:
a. Growth Factor Proteins – promote cell divison and
growth
 Compounds that stimulate nearby target cells to
grow and divide
 Numerous cells can be simultaneously receive
and respond to the growth factors produced by a
single cell in the vicinity
 Epidermal growth factors that stimulate
neighbouring skin cells to increase skin cell
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 division that results in increase of number of cells Long Distance Signalling
that form skin tissue
 Overall effect: abundance of cells, formation of
layers of cells in particular organ
b. Prostaglandin – affects metabolism of nearby cells
 First discovered in prostate gland
 After secretion, it is incorporated into semen and
affects motility of sperm cell
 Also secreted by all other animal cells
c. Nitric oxide – gas
 If secreted by white blood cells, it enhances the
formation of pseudopodia therefore enhancing
phagocytosis
 If secreted by neurons, it enhances release of
neurotransmitters
 If secreted by endothelial cells, it will affect the
neighbouring smooth muscles of tunica media
(middle layer of blood vessel); the muscles will
1. Endocrine (distant) Signalling
relax and the blood vessel lumen (cavity) will
 Use molecules called hormones
enlarge and there will be engorgement of blood
 Specialized cells release hormones that travel via
 Naging cure for erectile dysfuntion (viagra); 25
circulatory system to other parts of the body where
mg can cause 4 hr erection, di pwede for people
they reach target cells that can recognize and
with cardiovascular diseases
respond to them.
2. Synaptic signalling – occurs in animal nervous system  Hormones are produced in endocrine glands
 Endocrine glands are ductless (no neck for transport
of hormones to target cell)
 The hormones are transported by blood vessels from
the endocrine glands to the target cells
 The target cells have receptors that will receive the
hormones and exert the effects on the target cells
 The hormones are not limited to the endocrine glands
 Some neurons are also producing hormones
(neurosecretory cells)
 Plant hormones (plant growth regulation) sometimes
travel in plant vessels (tubes) but more often reach
their targets by moving though cells or diffusing
through the air as gas
 There is a space/synapse – narrow space  Examples: (like local regulators, hormones vary in
between nerve cell and target cell size and type)
 Pre-synaptic cell – neuron  plant hormone ethylene – gas that promotes fruit
 Post-synaptic cell – can be a neuron or muscle ripening and helps regulate growth. It is a
cell hydrocarbon of 6 atoms (C2H4), small enough to
 There are vesicles containing neurotransmitters pass through cell walls.
in the pre-synaptic cell  Mammalian hormone insulin – regulates sugar
levels in blood is a protein with thousand atoms
 In presense of stimulus, the vesicles will release
the neurotransmitter
 There will be receptors in the post-synaptic cell
that will bind with the neurotransmitter resulting in Three Stages of Cell Signaling
a cascade of events in post-synaptic cell  Earl W. Sutherland suggested that cells receiving signals
 Electrical signal along a nerve cell triggers the go through three processes (pathway of signaling)
secretion of neurotransmitter molecules. The  Sutherland and colleagues at Vanderbilt University
molecules act as chemical signals, diffusing investigated how animal hormone epinephrine triggers the
accros the synapse fight-or-flight response in animals by stimulating
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 breakdown of the storage polysaccharide glycogen within
liver cells and skeletal muscle cells (mobilization of fuel
reserves)
 Glycogen breakdown releases sugar glucose 1-phosphate
wich the cell converts to glucose 6-phosphate. Liver and
muscle cell can use this compound, an early intermediate
in glycolysis, for energy production
 Alternatively, the comopound can be stripped of
phosphate and released from the cell into the blood as
glucose which can fuel cells throughout the body
 Epinephrine stimulates glycogen breakdown by activating
cytosolic enzyme, glycogen phosphorylase
 Glycogen phosphorylase could be activated by
epinephrine only when hormone was added to intact cells.
 Epinephrine does not directly interact with enzyme
responsible for glycogen breakdown; steps or series are
occuring in the cell
 An intact membrane-bound cell must be present for
transmission of signal to take place.
 Reception
 Target cell’s detection of signaling molecule from
outside the cell
 Chemical signal is detected when signaling molecule
binds to receptor protein on cell’s surface (or inside of
cell)
 There are proteins in the membrane that have specific
configuration that would receive a specific substance
that is generally a chemical which is often reffered to
as a ligand.
 The ligand or substance fits to the receptor (very
specific)
 After binding, this will result to conformational
changes in the protein at the membrane.
 Transduction
 Binding of signaling molecule changes receptor in
some way initiating transduction
 This will stimulate neighboring proteins that will in turn
result to changes inside the cell called transduction
 Transduction stage converts the signal to a form that
can bring about specific cellular response (example:
binding of epinephrine to receptor protein on liver cell
leads to activation of glycogen phosphorylase)
 Sometimes occurs in a signal step but more often
required a sequence of changes in a series of
different molecules (signal transduction pathway) –
molecules in pathway are often call relay molecules
 Response
 Transduced signal triggers specific cellular response
 Cell-signaling process helps ensure that crucial
activities occur in the right cells at the right time and in
proper coordination with the activities of other cells of
the organism)
 Examples: catalysis by an enzyme, rearrangement of
cytoskeleton, activation of specific genes)
Reception
 Signalling molecule binds to a receptor protein
causing it to change shape.
 Receptor protein on or in the cell allows the cell to
hear the signal and respond to it
 Signalling molecules is complementary in shape to a
specific site on receptor and attaches there.
 The binding between a signal molecule (ligand –
molecule that specifically binds to another often larger
molecule) and receptor is highly specific (exact
shape)
 A shape change in a receptor is often the initial
transduction of the signal
 Most signal receptors are plasma membrane proteins
(most receptors are at the membrane)
 Most water-soluble signal molecules bind to specific
sites on receptor proteins that span the plasma
membrane (water-soluble molecules cannot readily
pass the phospholipid bilayer)
 Three main types of membrane receptors: (most
water-soluble signaling molecules bind to specific
sites on transmembrane receptor proteins that
transmit information from extracellular environment to
inside of cell)
1. G protein-coupled receptors (GPCRs)
 largest family of cell-surface receptors/eukaryotic
receptor proteins (more than 800 GPCRs) – yeast
mating factor, epinephrine, neurotransmitters, etc.
 single polypeptide has seven transmembrane a
helices
 specific loops between helices form binding sites for
signalling molecules (outside) and G protein (inside)
 A GPCR is a plasma membrane receptor that works
with the help of a G protein (protein that binds the
energy-rich molecule GTP)
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 The G protein acts as an on/off switch (control): If
GDP is bound to G protein, G protein is inactive
(guanosine diphosphate pag dinagdagan ng
phosphate magiging guanosine triphosphate; G
protein is associated with GDP)
 GPCR passes through the membrane seven times
(seven-(pass)-transmembrane domain receptors)
 In presence of inorganic phosphate, GDP will become
GTP and it will activate G protein that can bind to
GPCR
 GPCR will be activated and it can receive the ligand
 G protein will activate adjacent protein which will
result to other activations of nearby proteins
 Found only in eukaryotes
 Ligands that will bind to GPCR: light sensitive
compounds, odors, pheromones, hormones,
neurotransmitters
 Involved in many diseases (approx. 34% of modern
medicines are targeting these receptors) –
malfunction involved in human diseases including
bacterial infection
 Physiological roles:
 Gustatory sense (taste) – GPCRs in cells
meditate release of gustducin in response to
bitter and sweet tasting substances
 The sense of smell – Receptors of the olfactory
epithelium bind odorants (olfactory receptors)
and pheromones (vomeronasal receptors)
 Pheromones are organic compounds
responsible for a variety of smell
 Examples: Dogs have estrus cycle (heat
period) enlarged snout is vomeronasal organ
that is sensitive to pheromones. Female
dogs have high secretion of pheromones
when ovulating that tells male dog that she is
ready for copulation
 Humans also produce pheromones
(apocrine)
 Behavioral and mood regulation – receptors in
the brain bind several neurotransmitters like
serotonin (happy mood) and dopamine (memory,
motivation; decline results to Alzheimer’s)
 During inflammation – receptors such as
histamine receptors engage target cell types in
the inflammatory response
 Autonomic nervous system transmission – both
the sympathetic & parasympathetic NS
responsible for control of many automatic
functions of the body such as blood pressure,
heart rate and digestive processes
 Endocrine system – peptide and amino-acid
derivative hormones that bind to GPCRs on the
cell membrane of a target cell
 Hormones have two classes (lipids – can
pass through the phospholipid bilayer,
proteins – cannot pass through the
phospholipid bilayer without the aid of GPCR
 Embryonic development
2. Receptor tyrosine kinases (RTKs)/ Tyrosine kinase
receptors (TKRs)
 Have enzymatic activity
 Protein kinase – enzyme that catalyzes transfer of
phosphate groups from ATP to another protein
 Kinase – addition of phosphate, main activity is to add
phosphate
 Are membrane receptors that attach phosphates to
tyrosines (tyrosine – an amino acid, precursor of
different proteins, substrate protein)
 A receptor tyrosine kinase can trigger multiple signal
transduction pathways at once, helping the cell
regulate and coordinate many aspects of cell growth
and reproduction
 They normally exist as monomers. They have to be
dimers for them to function.
 They pair to form dimers
 Binding of signal molecule, receptor and dimer is not
yet the active form. It needs to be phosphorylated
(addition of ATP).
 Phosphorylated dimer – activated form of receptor
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 Activated receptor will now activate other proteins and
enzymes that will result to cellular function
 These receptors traverse the membrane only once
 Respond exclusively to protein stimuli
 Examples of ligands:
 Cytokines – enhance cell division
 Mitogenic growth factors – epidermal growth
factors, platelet derived growth factor
 Functions:
 Cell proliferation, differentiation
 Cell survival
 Cellular metabolism
 Participate in activity of abnormal cells (cancer cells)
 Critical role in the development and progression of
many types of cancer (yung gamot na gagawin should
block the receptor)
 Most receptors of cancer cells are TKRs  Example:
 Some RTKs have been discovered in cancer research  In the presynaptic cell are vesicles.
 Her2 – constitutively active form in breast cancer, Neurotransmitters are stored in the vesicles (the
patients have poor prognosis if tumor cells major neurotransmitter for vertebrates is
harbour excessive levels of HER2 acetylcholine). In the presence of stimulus, the
 EGF-R – overexpression in breast cancer gates of ion channels will open and the vesicles
will release acetylcholine in the synapse
 Kung walang stimulus, ion channels are closed
3. Ion channel receptor  Once acetylcholine diffuses from the presynaptic
cell to the synapse to the postsynaptic cell where
 Contains region that can act as gate
binding of acetylcholine and receptor takes place,
 Important in nervous system
this will result to the conformational change of the
 daanan ng ions, gated – hindi basta basta ion channel (it will open)
madadaanan. Yung ligand/signal ang magbubukas ng
gate
 A ligand-gated ion channel receptor acts as a gate
Biochemistry of Muscle Contraction
when the receptor changes shape
 When a signal molecule binds as a ligand to the  Presynaptic cell (usually nerve cell) which is
receptor, the gates allow specific ions such as Na+ or stimulated electrically that results to release of
Ca2+, through a channel in the receptor acetylcholine
 Ligand-gated ion channels = ionotropic receptors  Acetylcholine will have receptor in muscle. It will result
 Transmembrane channel protein which opens to allow to generation of action potential because Na+ will get
ions such as Na+, K+, Ca2- and or Cl- to pass through inside
the membrane in response to the binding of a  Action potential spreads along the cell membrane of
chemical messenger (i.e. a ligand) such as a the muscle.
neurotransmitter  normally the ligand that opens  When it reaches the triad through the transverse
the gate tubule, the action potential reaches the sarcoplasmic
 Malfunctions are associated to diseases (cancer, reticulum which normally stores calcium
heart disease, asthma)  Pag wala pang action potential, natatakpan binding
site ng regulatory protein (troponin complex,
tropomyosin) = no binding
 In the presence of calcium, calcium will bind with
troponin c which will result to the dislodge of the
regulatory protein = binding site is now available,
myosin can attach to actin (kabit)
 Myosin has partner (ADP) before attaching to actin

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Intracellular Receptors Signal Transduction Pathways
 Binding of signaling molecule to receptor plasma
membrane triggers first step
 Chain of molecular interactions that leads to particular
response in cell
 Molecules that relay a signal from receptor to response
(relay molecules) are often proteins
 Like falling dominoes, the receptor 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 shape change in a protein
 Original signaling molecule is not physically passed along

Protein Phosphorylation and Dephosphorylation

 Found in cytosol or nucleus of target cells

 Signalling molecules passes through the target cell’s
plasma membrane
 Small or hydrophobic chemical messengers (steroid and
thyroid hormones) readily cross the membrane
 Nitric oxide (NO) – another chemical signaling molecule
that possess an intracellular receptor, very small molecule
and readily passes between the membrane phospholipids
 Once hormone has entered cell, its binding to an
intracellular receptor changes the receptor into a
hormone-receptor complex that is able to cause a
response – in many cases, the turning on/off of particular
genes  Signal is transmitted by a cascade of protein
 Activated hormone-receptor complex can act as phosphorylations
transcription factor turning on specific genes  Protein kinases transfer phosphates from ATP to a protein
 Example (phosphorylation)
 Aldosterone – response happens in kidney, it acts as  Protein phosphatises remove phosphates from proteins
transcription factor and turns on specific genes that (dephosphorylation)
control water and sodium flow in kidney cells  Phosphorylation and dephosphorylation systems acts as a
 Testosterone – increases rate of proteinsynthesis in switch, turning activities on and off or up and down as
target cells, it is converted by intrecellular enzyme 5 a required
reductase to dihydrotestosterone (DHT) then it binds
to cytoplasmic receptor protein. This combination
moves to nucleus and initiates gene transcription and Small Molecules and Ions as Second Messengers
induces new protein formation
 Extra cellular signaling molecule that binds to receptor –
first messenger
Transduction: Cascades of molecular interactions relay signals  Second messenger – small, nonprotein, water-soluble ions
from receptors to target molecules in the cell that spread throughout a cell by diffusion, participate in
pathways initiated by GPCRs and RTKs
 Signal transduction involves multiple steps  Cyclic AMP and calcium ions (Ca2+)
 Multistep pathways can amplify a signal – each molecule
transmits signal to numerous molecules = geometric
increase
 Multistep pathways provide more opportunities for
coordination and regulation of the cellular response
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Cyclic AMP
 Binding of epinephrine to plasma membrane of liver cell
elevates cytosolic concentration of cyclic AMP (cAMP;
cyclic adenosine monophosphate)
 Adenyl cyclase (enzyme) convert ATP to cAMP in
response to extracellular signal (epinephrine)
 Phosphodiesterase converts cAMP to AMP (pag wala na
epinephrine)
 Immediate effect of elevation of cAMP levels is usally the
activation of serine/threoninbe kinase (protein kinase A)
 Protein kinase A - phosphorylates various proteins
 Examples:
 Cholera (Vibrio cholera) – toxin is an enzyme that
modifies G protein involved in regulating salt and
water secretion. GTP is stuck in active forming,
continuously stimulating adenyl cyclase
 cGMP – produced by muscle cell in response to NO
and causes relaxation of muscles
Calcium Ions and Inositol Triophosphate (IP3)
 Many of the signaling molecules (animals) induce
responses in target cells that increase cytosolic
concentration of calcium ions – more widely used than
cAMP
 can cause muscle cell contraction, exocytosis (secretion)
and cell division
 wide range of hormonal and environmental stimuli (plants)
can cause brief increase in calcium ions triggering
signaling pathways (greening response to light)
 cells use calcium ions as a second messenger in
pathways trigger by both GPCR and RTK
 calcium ion can function as second messenger because
concentration is cytosol is lower than outside the cell.
Calcium concentration is high in ER because they are
imported there
 signal relayed may trigger increase in calcium in cytosol
 pathways leading to release of calcium involve inositol
triophosphate (IP3) and diacylglycerol (DAG) – they are
produced by cleavage of certain phospholipid in plasma
membrane
Nuclear and Cytoplasmic Responses
 Ultimately, a signal transduction pathway leads to the
regulation of one or more cellular activities
 The response may occur in the cytoplasm or in the
nucleus
 Many signaling pathways regulate synthesis of enzyme or
other proteins by turning genes on or off in the nucleas
(final activated molecule in signaling pathway may function
as transcription factor)


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 Signaling pathway can also regulate activity of proteins.
This directly affects proteins that function outside the
nucleus.
 Signaling pathways can also affect overall behaviour of
cell(changes in cell shape)
Regulation of the Response/Fine tuning of response
 Response is not simply turned on or off. Rather, the extent
and specificity of the response are regulated in multiple
ways.
1. Signal Amplification
 Elaborate enzyme cascades amplify the cell’s
response to a signal
 Number of activated product is much greater than
preceding step
2. The Specificity of Cell Signaling and Coordination of the
Response
 Different kinds of cells have different collection of proteins
 Different proteins allow cells to detect and respond to
different signals
 Even the same signal can have different effects in cells
with different proteins and pathways
 Pathway branching and “cross-talk” further help the cell
coordinate incoming signals
3. Signaling Efficiency: Scaffolding Proteins and Signaling
Complexes
 Scaffolding proteins are large relay proteins in which
other relay proteins are attached
 Scaffolding proteins can increase the signal
transduction efficiency by grouping together different
proteins involved in the same pathway
 In some cases, it may also help activate some relay
proteins
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4. Termination of Signal
 Inactivation mechanisms are essential aspect of cell
signaling for a cell to be capable of responding to
incoming signals
 Binding of signal molecules to receptors is reversible
 If ligand concentration falls, fewer receptors will be
bound
 Unbound receptors revert to an inactive state
 Cellular response only occurs when the concentration
of receptors with bound signaling molecules is above
a certain threshold
Apoptosis integrates multiple cell-signaling pathways
 Signaling pathway components interact with each other in
various ways
 Apoptosis – programmed or controlled cell suicide
 Cells that are infected, damaged or have reached end of
functional life span undergo apoptosis
 During the process, components of the cell are chopped
up and packaged into vesicles that are digested by
scavenger cells
 Apoptosis protects neighboring cells
 Apoptosis prevents enzyme from leaking out of a dying
cell and damaging neighboring cells
 Signal that triggers apoptosis can come from inside or
outside the cell
Apoptosis Pathways and the Signals That Trigger Them
 Caspases – main proteases (proteins that cut up proteins)
that carry out apoptosis
 About 15 diff. caspases can carry out apoptosis
 Apoptosis can be triggered by:
 Extracellular death signaling ligand
 DNA damage in nucleus (irreparable)
 Protein misfolding in endoplasmic reticulum
 Apoptosis evolved early in animal evolution and is
essential for the development and maintenance of all
animals
 In vertebrates, apoptosis is essential for normal
development of the nervous system, immune system and
morphogenesis of hands and feet
 Level of apoptosis is lower in ducks and other water birds
 Low level of apoptosis in humans cause webbed fingers
and toes
 Apoptosis may be involved in degenerative nervous
system diseases (Parkinson’s and Alzheimer’s) –
accumulation of aggregated proteins in neuronal cells
activates an enzyme that triggers apoptosis resulting in
loss of brain function
 Apoptosis may also contribute to cancer

Apoptosis in the Soil Worm Caenorhabditis elegans

 Apoptosis is important in shaping an organism during
embryonic development
 Apoptosis is triggerd by signals that activate a cascade of
“suicide” proteins in the cells destined to die
 Apoptosis results when proteins that “accelerate”
apoptosis override those that “put the break” on apoptosis
 Ced-4 and Ced-3 –proteins involved in apoptosis
 Ced-9 –master regulator of apoptosis, act as break in
absence of signal
 Main proteases of apoptosis are called caspases
 Chief caspase is Ced-3 protein

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