Download Signalling Molecules and Signal Transduction

Signalling Molecules
and
Signal Transduction
Signalling molecules
• The cells of an organism are constantly
receiving information about their surrounding
environment in order to control and regulate
their activities.
• Cells also need to communicate to other cells to
ensure the control and regulation of systems
within the organism.
• Molecules that enable cells to receive
information and communicate with other cells
are called signalling molecules or ligands.
Receptors
• For a cell to act on and respond to a chemical
signal the cell must have a receptor to receive
the signal.
• Once the signalling molecule has interacted with
the receptor, the information needs to be
processed to produce the appropriate cellular
response.
• Signal processing within a cell may involve a
series of molecular steps called a signal
transduction pathway.
Types of signals
• There is constant ‘chemical chatter’ between
cells in multicellular organisms.
• Chemical signals can be classified according to
the distance the signal needs to travel:
– Autocrine signals – a cell secretes signalling
molecules that can bind to its own receptors.
– Paracrine signals – signals are released by cells into
the extracellular medium in their neighborhood and
act locally
– Endocrine signals – signals produced in endocrine
glands are secreted into the bloodstream and can be
distributed throughout the body
Types of signals
Types of Signalling Molecules
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•
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Hormones
Neurotransmitters
Pheromones
Plant hormones
Hormones
• Production
– Usually produced in endocrine glands.
– Some neurons also produce hormones e.g. the
neurons of the hypothalamus
• Transport
– Travel in the general circulation (blood) or tissue fluid.
• Targets
– Specific cells in the body respond to each hormone.
– Target cells have a specific receptor for each
hormone they respond to.
Types of hormones
• The chemical nature of a hormone
influences the way it interacts with its
target cells.
• Based on chemical structure hormones
can be divided into three types.
– steroid hormones
– peptide hormones and protein hormones
– amino acid derivatives
Steroid Hormones
• Are synthesised on demand from
precursors in a cell.
• Leave the cell by simple diffusion.
• Have a long life span.
• Examples include: testosterone,
oestrogen, progesterone and
corticosteroids, all of which are
synthesised from cholesterol.
Peptide/Protein hormones
• Peptide hormones (< 200 amino acids) and
protein hormones (> 200 amino acids).
• Made in advance by a cell and stored in
secretory vesicles.
• Leave the cell by exocytosis.
• Have a short life span.
• Examples of peptide/protein hormones include:
adrenaline, thyroxine, oxytocin, antidiuretic
hormone (ADH) and growth hormone
Amino acid derivative hormones
• Small molecules structurally related to a
simple amino acid; for example, thyroid
gland hormones are derived from tyrosine.
• Made in advance by a cell and stored,
some in precursor form, in secretory
vesicles until required.
• Leave the cell by exocytosis or, if a
precursor, by simple diffusion.
• Have a short life span.
Key differences in hormones
• Steroid hormones
– Have a lipid base, hence they are lipophilic and insoluble in water.
– Require a carrier protein for transport by blood, which has a water
base.
– Lipophilic nature allows steroid hormones to pass through cell
membranes that are phospholipid in nature.
• Amino acid hormones, peptide and protein hormones
– Are water-soluble hormones and therefore hydrophilic.
– Require no assistance to travel in the bloodstream.
– Hydrophilic nature means they are unable to pass through phospholipid
membranes without assistance.
– Water-soluble hormones require the presence of a second messenger
molecule, such as G protein, to transmit their message from the
surface membrane receptor into the cytosol.
Signalling by hormones
• Lipid-soluble hormones pass
through the cell membrane and
bind to receptors in the
cytosol.
• Water-soluble hormones bind
to receptors in the cell
membrane and stimulate
second messenger systems.
• In both cases, the signals
received by the cells go through
a cascade of changes, called
signal transduction, and finally
the cell initiates its response.
Second messenger systems
• Receptors associated with second messenger
systems include G protein-coupled receptors,
tyrosine-kinase receptors, and ion-channel
receptors.
• The ligand binds to a receptor on the cell's
plasma membrane activating an associated
molecule (the second messenger).
• The second messenger activates other
intracellular molecules that elicit a response.
Second messenger systems
Neurotransmitters
• Most are peptides or modified amino acids
• Production
– Produced in neurons and stored in synaptic vesicles
• Transport
– Synaptic vesicles fuse with cell membrane following
an electrical signal, and neutrotransmitters are
released. The contents of the synaptic vesicles
diffuse across the synaptic gap.
• Targets
– Dendrites of another neuron in order to continue an
impulse
– Cells stimulated by neurons (muscles, glands)
Neurotransmittors
• A nerve ending in the region of a synapse with another cell, contains
numerous mitochondria and many tiny vesicles containing
neurotransmitter molecules.
• When an action potential enters the nerve ending, the vesicles move
to the cell membranes and release their contents into the synaptic
gap.
• These molecules diffuse across the gap to interact with specific
receptors on the postsynaptic cell membrane.
Neurotransmitters
• Neurotransmitters
cannot pass through the
plasma membrane.
• They interact with a
receptor on the cell
surface which opens a
protein channel and
allows Na+ (sodium ions)
to enter the cell and
change the membrane
potential (important for
electrochemical
potential).
Pheromones
• May be simple modified hydrocarbons or more
complex molecules
• Production
– Produced in exocrine glands
• Transport
– Molecules are secreted into the external environment.
• Targets
– Other members of the same species. Animals of
different species either don’t detect them or don’t
respond to them.
Using pheromones against insect
pests
a)
b)
c)
d)
Normal zig-zag tracking of male
moth along wafting stream of
pheromone.
The confusion strategy involves
flooding an area with
pheromone so that males
become confused and cannot
find female moths.
Pheromone baits can lure moths
into traps, reducing the size of
the current population.
A few baited traps can be used
to monitor the size of a moth
population in order to determine
whether further action is
required.
Plant Hormones
• Vary from simple organic molecules like ethylene to large
complex organic molecules.
• Production
– Produced by specialized cells in a variety of plant tissues.
• Transport
– Generally by the plant’s vascular tissue
– Ethylene is a gas and is able to diffuse through intercellular
spaces.
• Targets
– Cells which have receptors for the particular hormone.
– One hormone can affect a variety of plant tissues.
Signal Transduction
• Signal transduction refers to the way that
receptors on the cell surface convert incoming
signals into information leading to an
appropriately coordinated response.
• The binding of a signalling molecule with it
specific receptor initiates a cellular response.
• Like homeostasis, the action of signalling
molecules can be understood in terms of the
stimulus response model.
• The binding of the signalling molecule to the
receptor affects cellular chemicals.
• Changes in chemical activity in a cell cause
changes in function.
SIGNAL
SIGNAL
TRANSDUCTION
APOTOSIS
GROWTH
SURVIVAL
DIFFERENTIATION
MIGRATION
PROLIFERATION
Signal transduction
cascades are the nervous
system of the cell
The basics of signal transduction
• Signal is received.
• Signal is amplified.
• Response is usually a
change in protein levels or
associations.
• Specificity possible at all
levels.
• Feedback possible.
• Conservation between
many organisms . . . and
pathways
Signal transduction amplifies the
original signal
• The below-surface receptors activated by steroids and the G or
other proteins activated as a result of water-soluble hormones both
trigger a cascade of events.
• These events generally involve proteins and ultimately lead to a
biological response within the cell relevant to the original
hormone signal.
• This process in which a cell converts one kind of signal into another,
by a series of relay molecules and other proteins, is called signal
transduction.
• Within a cell, signal transduction amplifies the signal that the
original hormone molecule brought to the cell.
• A signal brought by a single hormone molecule or a few hormone
molecules can be amplified through many steps to induce reactions
that involve many substrates.
• Binding of antigen
to a B cell receptor
transduces a signal
which upregulates
transcription of
genes important in
proliferation of B
cells.
• It can be seen that
transduction of the
signal is a nonlinear process.
IMPORTANT CONCEPT:
Signaling is nonlinear! Think of signal transduction as
a web not a line . . .
Responses to Signals
• Activation of genetic material, DNA.
• May lead to the production of proteins, including
enzymes.
• Enzymes become involved in a range of metabolic
reactions within the cell.
• Response may be the production of another hormone
that will leave the cell and carry different kinds of signals
to other cells.
• Alternatively signals may suppress the production of
proteins, including enzymes and therefore down-regulate
particular metabolic reactions within the cell.
Apoptosis
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•
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Apoptosis occurs in response to particular cell signals.
Also known as programmed cell death (PCD), apoptosis is a normal part of
the life of cells.
Cell death is important for:
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–
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Developmental changes in growing embryos
Ridding tissues of old, infected or damaged cells
Removing immune cells which attack “self”
Removing cells which have sustained DNA damage so that they do not continue
to reproduce and form cancers
•
Too little apoptosis can lead to cancer and too much can cause
degenerative diseases such as Alzheimer disease.
•
Cell death occurs when the cell membrane shrinks, DNA fragments and
lysosomes empty their contents into the cell causing the cellular
components to be broken down. The dead cell is then consumed by
phagocytes.