Path 10020: Basic Principles of Cell Biology

Cell Communication & Cell

Signalling Lecture 1

Professor Catherine Godson

Diabetes Complications Research Centre
Conway Institute & School of Medicine

Essential Cell Biology, Alberts et al.,

[email protected]
Cell Communication and Cell Signaling

• Principles of inter-cellular communication

• Molecular mechanisms of cellular reception and
response to extracellular signals … signal
transduction
• When signalling goes awry…e.g. Diabetes
• Review of Cell Signaling
• Innate Immunity
How do cells receive, process and
respond to extracellular signals?
You already know….and need to keep in
mind
• Cell membrane/Plasma membrane: protein and lipid

• Eukaryotic cells contain internal membranes e.g. ER

[endoplasmic reticulum], lysosomes,mitochondria

• Proteins are modified by several mechanisms including

PHOSPHORYLATION

• Phosphorylation of the amino acids tyrosine, serine and

threonine are very important

• Transcription factors bind DNA

• DNA makes RNA makes PROTEIN

Common mechanisms underlie cell
communication
• Cell communication is an essential feature
enabling organisms to respond appropriately to
environmental cues:
– nutrient availability, mating, requirement for
oxygen
• Cells typically communicate with each other by
chemical signals
• The mechanisms by which cells
– Receive
– Process
– Respond
to signals is highly conserved
from microbes to man
Are bacteria loners?
Are bacteria loners?

• Colonies of bacteria can generate a coordinated

response
• Dependent on cell density bacteria can produce
signals…. once above a certain threshold this
can alter behaviour [gene expression]
• Quorum sensing: allows individual bacteria
within colonies to coordinate and carry out
colony-wide functions such as: sporulation,
bioluminescence, virulence and biofilm formation
Are bacteria loners?

S.Aureus biofilm on surface of a catheter

Signalling in eukaryotes e.g: Mating in
yeast
Yeast mating cell a-factor
• a and a are two types of a Receptor
yeast
• Secrete mating factors a a
which bind to receptors
Receptor
on complementary cells a-factor
a Yeast mating cell a
• Cells respond to receptor
binding and activation
a a
• The mating signal is
transduced and the
cells fuse

a/a
 Mating in yeast
• These eukaryotic
communication processes are
prototypic of signal
transduction in multicellular
organisms a a

• Stimulus
• Secretion
a

• Recognition a a

• Response

a/a
Fight or Flight…. Hyperarousal
• Increase heart rate and
blood pressure
• Dilation of pupils
• Veins contract, blood
diverted from skin
• Muscles tense [goose
bumps]
• Smooth muscles relax,
increase oxygen
• Blood glucose increases
• Non-essential functions
shut down
Adrenaline [aka Epinephrine] is released
from the adrenal medulla and acts on
specific targets including:

Heart: Rate and force of contraction

Liver: Glycogen breakdown to release glucose
Lung: Inc breathing
GI: Vasoconstriction
Muscles: Vasodilation

One signal is generating multiple

responses
Signals can act over a long or short
range e.g. endocrine signalling
• Endocrine cell receives a
stimulus
• Secretes a hormone into
circulation
Endocrine cell
• Hormone binds to specific
receptors on target cells
• Receptors can be on cell
Blood vessel surface or can be in the
cytoplasm [steroid
receptors] or nucleus
• Elicits a physiological
response
• E.g. Insulin secreted from
pancreas acts on targets in
muscle, adipose
Neuronal signalling

• Signal is relayed along

axons
• Electrical signals reach
the axon terminal and
causes a pulse of
neurotransmitter release
across the synapse
• The neurotransmitter
elicits a response on the
target cell
• E.g: neurotransmitter
release from the phrenic
nerves acts on targets
cells in diaphragm
Signals can act over a long or short
range e.g. paracrine signals act locally

• e.g. Growth factors are

produced and act on
local target cells that
express growth factor
receptors
• In low oxygen [hypoxia]
a growth factor [VEGF]
is produced and
stimulates proliferation
of endothelial cells and
formation of new blood
vessels and oxygen
delivery
Nobel Laureates Physiology or Medicine, 2019
Autocrine signals act locally

• The signalling molecules are produced and secreted by

the cells on which they act
• E.G. Interleukin-1 is produced by monocytes and acts
on the IL-1 receptor, important in regulating
inflammation
Cell-cell contact dependent: juxtacrine
signalling

• Cell-cell recognition: NB in
immune response direct
interaction between
different cell types, in
development.
• No secreted signal

Cell-cell recognition
JUXTACRINE
Cells respond selectively to signals

• Cells are typically exposed to multiple signals yet

respond to a limited number of specific signals
• Response of a cell to a signal depends on the presence
of a specific receptor and intracellular molecules
• Receptors are typically highly specific for a particular
signal
• Responses to a few signals can change numerous
aspects of a cell’s ‘behaviour’: shape, movement,
metabolism, gene expression
• The response from a cell surface receptor is relayed
into the cell by intracellular signalling molecules that
activate effector proteins… next lectures
Signals and receptors can be extracellular
or intracellular
What are the signals?
Note chemical and size diversity
What are the signals?
Same signal, different responses

The signal alone does not dictate the response:

how the target cell receives and interprets the signal is critical
[and as we saw earlier with adrenaline]
Signals and receptors can be extracellular or
intracellular

• Small and or hydrophobic

signals diffuse across
plasma membrane and
activate intracellular
enzymes or bind to
intracellular receptors
• e.g. steroid hormones
activate intracellular
receptors
• e.g. Nitric oxide, NO
diffuses into cell and
regulates enzyme activity
causing muscle relaxation
Small hydrophobic hormones bind
intracellular receptors
Steroids bind to intracellular receptors
and regulate transcription
• Steroid receptors are termed
‘nuclear receptors’
• When not bound by steroid
hormone most are cytosolic. R
translocates to nucleus when
activated by ligand i.e.steroid
• Steroid-R complex act as a
transcription factor, binds DNA
and regulates transcription
• mRNA is transcribed, protein
translated
• Typically we describe steroid
receptor activation in terms of
genomic effects, some evidence
of short term non genomic
effects too [acting more like an
extracellular signal]
• NUCLEAR RECEPTORS
Anabolic steroids:
• Increase muscle mass
• Decrease muscle
breakdown
• May have use in
treating cachexia
Testicular feminization:
• Androgen/Testosterone
R cannot respond to
hormone so that
genetically male
individuals are
externally female
• Also mutations in
production of active
testosterone e.g.
enzyme deficiencies eg
5a-OH-reductase
Cortisol signaling
 In summary:

Hydrophobic molecule eg a steroid hormone

binds to a receptor and the steroid-receptor
complex act as transcription factors and ‘turn
on’ gene expression [can also ‘turn off’]
Cellular responses to signals can be fast
or slow

Millisecond responses to
epinephrine
 In conclusion
• Integration of responses to various stimuli is vital
for survival of organism
• This is achieved through cell-cell communication
by mechanisms that include local signalling
between cells and long distance signalling
• SPECIFICITY is vital