Cellular Communication and Cell Receptors

CELL RECEPTORS AND
SIGNAL TRANSDUCTION
INTRACELLULAR SIGNALING: Signal Transduction
Types of Cell Signaling
There are various

possible types by which
cells can communicate
with each other.
1. Paracrine
2. Autocrine
3. Endocrine
4. Juxtacrine
5. Synaptic
✓ Extracellular signaling
molecules released by
cells occurs over distances
from a few microns –
autocrine (c) and paracrine (b)
signaling to several meters in
endocrine (a) signaling.
✓ In some instances,
receptor proteins attached to
the membrane of one cell interact
directly with receptors on an
adjacent cell (d).
Juxtacrine communication (contact-dependent signalling)
It is the communication through cell adhesion to growth factors expressed on cell surface. Cells
transmit signal via membrane bound signal molecule to receptors on target cells that are in
direct contact.
Examples:
Growth factors
Cytokines
Chemokines
Synaptic Transmission
A synapse is a site where information is transmitted
from one cell to another
Two main classes:
– Electrical synapses
• Electrical synapses allow current to flow from one excitable cell to
the next via low resistance pathways between the cells called gap
junctions (i.e.; cardiac muscle, some kinds of smooth muscle like
uterus or bladder).
– Chemical synapses
• In chemical synapses, there is a gap between the presynaptic cell
membrane and the postsynaptic cell membrane, known as the
synaptic cleft. Information is transmitted across the synaptic
cleft via a neurotransmitter, a substance that is released from the
presynaptic terminal and binds to receptors on the postsynaptic
terminal.
Electrical Synapses
– Direct transfer of ionic
current from one cell to the
next
– Gap junction
• The membranes of two
cells are held together by
clusters of connexins
• Connexon
– A channel formed by six
connexins
• Two connexons combine to
form a gap junction
channel
– Allows ions to pass from
one cell to the other
– 1-2 nm wide : large enough
for all the major cellular
ions and many small
organic molecules to pass
• Cells connected by gap junctions are said to be ‘electrically
coupled’.
• Flow of ions from cytoplasm to cytoplasm
bidirectionally
• Very fast, fail-safe transmission
– Often found where normal function requires that the
neighboring neurons be highly synchronized
– Common in mammalian CNS as well as in invertebrates
– Electrical coupling of neurons has been demonstrated for
most brain regions, including the inferior olive, cerebellum,
spinal cord, neocortex, thalamus, hippocampus, olfactory
bulb, retina, and striatum.
Chemical Synapses
– Synaptic cleft : 20-40 nm wide

(gap junctions : 4 nm)
– Adhere to each other by the
help of a matrix of fibrous
extracellular proteins in the
synaptic cleft
– Presynaptic element (= axon
terminal) contains synaptic
vesicles
– Membrane differentiations
• Active zone
• Postsynaptic density
Chemical Synapses Electrical synapses
Principles of Chemical Synaptic Transmission
• Basic Steps
– Neurotransmitter
synthesis
– Load neurotransmitter into
synaptic vesicles
– Vesicles fuse to
presynaptic terminal
– Neurotransmitter spills
into synaptic cleft
– Binds to postsynaptic
receptors
– Biochemical/Electrical
response elicited in
postsynaptic cell
– Removal of
neurotransmitter from
synaptic cleft
Receptors
• Follow the same binding rules;
– Chemical specificity
– Competition
– Saturation
– Affinity
• A single type of receptor for a particular
messenger may elicit a totally different
response in different cell types
Regulation of receptors
• Up-regulation and down-regulation are made possible
because there is a continuous degradation and synthesis of
receptors.
• The main cause of down-regulation of plasma-membrane
receptors is as follows:
– The binding of a messenger to its receptor can stimulate the
internalization of the complex; that is, the messenger
receptor complex is taken into the cell by endocytosis (an
example of so-called receptor-mediated endocytosis).
– This increases the rate of receptor degradation inside the
cell.
– Thus, at high hormone concentrations, the number of
plasma-membrane receptors of that type gradually decreases
during down-regulation.
• The opposite events also occur and contribute to up-
regulation.
– The cell may contain stores of receptors in the
membrane of intracellular vesicles; these are then
inserted into the membrane via exocytosis during up-
regulation.
• Another important mechanism of up-regulation and
down-regulation is alteration of the expression of the
genes that code for the receptors.
Intracellular receptors:
- signaling molecules include;
steroid hormones, retinoids,
thyroxine, etc
- receptor-hormone complex
acts a transcription factor
to alter transcription of certain
genes
Membrane (Cell surface) receptors:

- signaling molecules include;
peptide hormones, catecholamines, insulin,
growth factors, cytokines, etc
- binding, and subsequent events;

triggers an  or  in the cytosolic
concentration of a second messenger; or the
activated, bound receptor acts as a scaffold
to recruit and activate other intracellular
proteins
Steroid Hormone Receptors
Ionotropic receptors
✓ Ligand (Transmitter)-
gated ion channels
✓ Ligand-binding causes a
slight conformational
change that
leads to the opening of
channels
✓ Not as selective to ions
as
voltage-gated channels
✓ Depending on the ions
that can
pass through, channels are
either
excitatory or inhibitory
Metabotropic receptors
• G-protein-coupled receptors
• Trigger slower, longer-lasting and more diverse postsynaptic

actions
• Same neurotransmitter could exert different actions

depending on receptor subtype

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Cellular Communication and Cell Receptors

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CELL RECEPTORS AND

There are various

– Synaptic cleft : 20-40 nm wide

Membrane (Cell surface) receptors:

- binding, and subsequent events;

• Trigger slower, longer-lasting and more diverse postsynaptic

• Same neurotransmitter could exert different actions

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