CHAPTER 11
CELL COMMUNICATION
Types of cell talk
• Local ‘talk’: Paracrine Signaling (local secretions from
neighboring cells), direct cell to cell ‘talk’/via diffusible
substances. Ex: growth factors, ethylene gas (plants)
• Long-distance ‘talk’: Synaptic (electrical or chemical
neuron ‘talk’) signaling, Hormones released into the
blood by endocrine glands (ex: epinephrine).
Growth Factors - increase cell
division; excess = cancer
• Local ‘talk’: Paracrine Signaling (local secretions from
neighboring cells), direct cell to cell ‘talk’ via diffusible
substances. Ex: growth factors, ethylene gas (plants)
• Long-distance ‘talk’: Synaptic (electrical or chemical
neuron ‘talk’) signaling, Hormones released into the
blood by endocrine glands (ex: epinephrine).
Cancer
Ethylene gas = ripening of fruit
• Local ‘talk’: Paracrine Signaling (local secretions from
neighboring cells), direct cell to cell ‘talk’/via diffusible
substances. Ex: growth factors, ethylene gas (plants)
• Long-distance ‘talk’: Synaptic (electrical or chemical
neuron ‘talk’) signaling, Hormones released into the
blood by endocrine glands (ex: epinephrine).
Synaptic talk involves release of
neurotransmitters
• Local ‘talk’: Paracrine Signaling (local secretions from
neighboring cells), direct cell to cell ‘talk’/via diffusible
substances. Ex: growth factors, ethylene gas (plants)
• Long-distance ‘talk’: Synaptic (electrical or chemical
neuron ‘talk’) signaling, Hormones released into the
blood by endocrine glands (ex: epinephrine).
Hormones - FIGHT or FLIGHT!
• Local ‘talk’: Paracrine Signaling (local secretions from
neighboring cells), direct cell to cell ‘talk’/via diffusible
substances. Ex: growth factors, ethylene gas (plants)
• Long-distance ‘talk’: Synaptic (electrical or chemical
neuron ‘talk’) signaling, Hormones released into the
blood by endocrine glands (ex: epinephrine).
Epinephrine Hormone Action
• One action of Epinephrine = Increase in breakdown of
glycogen (polysaccharide) in liver to glucose (why?)
• Epinephrine is secreted by adrenal gland (top of
kidney), moves through blood, reaches liver
• Epinephrine cannot DIRECTLY break down glycogen in
a test tube!
The process of epinephrine action (in general cell
communication) must involve three stages.
1)Reception - a chemical signal binds to a cellular protein called
receptor, typically at the cell’s surface (or in cytoplasm).
2)Transduction- binding leads to a change in the receptor that
triggers a series of changes along a signal-transduction
pathway
3)Response = a specific cellular activity ex: glycogen breakdown.
Fig. 11.5
1) Reception - signal molecule is referred to as “ligand” - usually
a small molecule ex: epinephrine/adrenaline
Receptor - can be on cell surface (or cytoplasm - ex. steroids).
Ligand shape FITS receptor perfectly! (=> SPECIFICITY)
Fig. 11.5
Signal transduction
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2) Receptors can be linked to G proteins
- When ligand (ex. Epinephrine) binds to receptor,
what follows is SIGNAL TRANSDUCTION (multistep)
G proteins are like on-off switches - when GTP is
bound = ACTIVE; GDP is bound = INACTIVE
2) G-protein signal transduction system
Receptor + Epinephrine = G protein binds to receptor
• G protein is activated (GTP attaches).
• Activated G protein binds with another membrane protein,
(Adenylyl Cyclase - an enzyme). This enzyme is ‘activated’
leading to a cellular response or more signal transduction !
• Signal Transduction…….
• Adenylyl cyclase converts ATP to cAMP (cyclic
AMP).
• cAMP is short-lived as another enzyme phosphodiesterase converts it to AMP (shutting
off switch!).
• cAMP is referred to as a SECOND MESSENGER
Fig. 11.12
• Signal Transduction……. More generally, many
hormones and other signals trigger the formation of
cAMP.
• Binding by the signal to a receptor activates a G protein that
activates adenylyl cyclase in the plasma membrane.
• The cAMP from the
adenylyl cyclase
diffuses through the
cell and activates
protein kinase A
which phosphorylates
other proteins.
Fig. 11.13
* Phosphorylation of proteins by a specific enzyme (a protein
kinase) is a widespread cellular mechanism for regulating
protein activity. Phosphorylation by ‘kinases’ activates (ON),
dephoshorylation by ‘phosphatases' inactivates (OFF)!
Fig. 11.11
3) Cellular Response
-
Signal-transduction pathway
leads to the regulation of
one or more cellular
activities. For example,
epinephrine helps regulate
cellular energy metabolism
by activating enzymes that
catalyze the breakdown of
glycogen. One molecule of
epinephrine produces a
billion fold increase in the
number of phosphorylase
enzymes that breakdown
glucose. This billion fold
increase is possible due to
the signal transduction
pathway. Also having a
multi-step signal ransduction
pathway helps control the
cellular response better by
having different agents fine
tune it!
• Cellular Response….other
ligands act in different ways
• Other signaling pathways do
not regulate the activity of
enzymes but the synthesis of
enzymes or other proteins.
• These can turn specific genes
on or off in the nucleus.
Fig. 11.17
• Cellular Response….
• Example: Steroids
(testosterone) bind directly
to 1) receptors in the
cytoplasm and this 2)
activates proteins
(transcription factors) that 3)
turn ON/OFF genes!
Fig. 11.17
• Cellular Response……variations
• Epinephrine triggers liver or striated muscle cells to break
down glycogen, but cardiac muscle cells are stimulated to
contract, leading to a rapid heartbeat.- WHY? And HOW?
Muscle Contraction involves
Increase in Calcium Ions
- Two of the most important
second messengers are cyclic
AMP and Ca2+.
- Ca2+ concentration is much
lower inside than outside
the cell.
- Various protein pumps
transport Ca2+ outside the
cell or inside the
endoplasmic reticulum
or other organelles.
- Signal-transduction pathways trigger the release of
Ca2+ from the cell’s ER.
• The pathways leading to release involve still other
second messengers, diacylglycerol (DAG) and
inositol trisphosphate (IP3).
• Both molecules are produced by cleavage of certain
phospholipids in the plasma membrane.
• DAG and IP3 are created when a phospholipase
cleaves a membrane phospholipid PIP2.
• Phospholipase may be activated by a G protein or a
tyrosine-kinase receptor.
• IP3 activates a gated-calcium channel, releasing Ca2+.
Fig. 11.15
• Cholera - acts by modifying G proteins!
• Shutting off G proteins:
• The G protein can also act as a GTPase enzyme and
hydrolyzes the GTP, which activated it, to GDP.
• This change turns the G protein off.
• The whole system can be shut down quickly when the
extracellular signal molecule is no longer present.
Fig. 11.7c
• Other types of receptors are not linked to G
proteins. Receptors may be tyrosine kinases:
• A individual tyrosine-kinase receptor consists of
several parts:
• an extracellular signal-binding sites,
• a single alpha helix spanning the membrane, and
• an intracellular
tail with several
tyrosines.
Fig. 11.8a
• When ligands bind to two receptors polypeptides,
the polypeptides aggregate, forming a dimer.
• This activates the tyrosine-kinase section of both.
• These add phosphates to the tyrosine tails of the
other polypeptide.
Fig. 11.8b
• The fully-activated receptor proteins activate a
variety of specific relay proteins that bind to
specific phosphorylated tyrosine molecules.
• One tyrosine-kinase receptor dimer may activate ten or
more different intracellular proteins simultaneously.
• These activated relay
proteins trigger many
different transduction
pathways and
responses.
Fig. 11.8b
• More receptors:
• Ligand-gated ion
channels are protein pores
that open or close in
response to a chemical
signal.
• This allows or blocks ion flow,
such as Na+ or Ca2+.
• Binding by a ligand to the
extracellular side changes the
protein’s shape and opens the
channel.
• Ion flow changes the
concentration inside the cell.
• When the ligand dissociates,
the channel closes.
Cell signaling evolved early in
the history of life
• Sex is a really important topic of cell talk!
• Rather than relying on diffusion of large relay
molecules like proteins, many signal pathways
are linked together physically by scaffolding
proteins.
• Scaffolding proteins may themselves be relay proteins
to which several other relay proteins attach.
• This hardwiring
enhances the speed
and accuracy of
signal transfer
between cells.
Fig. 11.19