Cells, such as the ones in the

human body, need a way to to do it cells often send out

interact and communicate with tiny chemical
substances such as hormones, signals that act on the receptors
drugs, or even sunlight. That is on other
where cellular receptors come cells.
in.
Cellular receptors are proteins Signals can be classified
which are essential for cell according to the
signaling. When a specific distance between the signaling
signaling molecule (ligand) cell and the
binds to its corresponding target cell.
receptor, this acts like a key
unlocking a door. The binding Autocrine signals are produced
of a ligand triggers a change in by a cell and
the receptor, which leads to a go to its own receptors, so the
host of downstream signaling cell sends
actions and changes inside the
cell. a signal to itself.
A receptor is a protein
molecule in a cell or on the Paracrine signals are produced
surface of a cell to which a by a cell and
substance (such as a hormone, go to target cells that are
a drug, or an antigen) can bind, nearby.
causing a change in the activity
of that cell. And endocrine signals are
produced by a cell
To make a multicellular and go to target cells that are
organism, cells must further away.
be able to communicate with
one another, and
Examples of these include
hormones that are
secreted into the bloodstream,
as well as
cytokines that can be released
at the site
of injury and act on the brain
to cause a
fever.
Signaling molecules or ligands
can be hydrophobic,
meaning that they tend to repel
water, or
hydrophilic, meaning that they
tend to stay
in water.
Hydrophobic signalling
molecules can’t freely
float in the extracellular space,
so they’re
brought to the target cells by
carrier proteins.
Hydrophobic molecules can
diffuse across the
cell membrane and bind to
receptor proteins
inside the target cell - either in
the cytoplasm
or in the nucleus.
Most signal molecules are
hydrophilic, so
they can freely float in the
extracellular
space to reach the target cells,
but are then
unable to cross the cell
membrane.
So to pass on the signal,
hydrophilic molecules
bind to receptors on the cell
surface.
These receptors are
transmembrane proteins,
with an extracellular end that
binds to the
ligand, and an intracellular end
that triggers
a signaling pathway inside the
cell.
 receptors, enzyme-coupled
We can think of the cell receptors, and ion
signaling pathway channel receptors.
in three stages.
G-protein coupled receptors
The first stage is reception, are seven pass
which is when transmembrane receptors.
the target cell’s receptor binds
to a ligand. These are really long proteins
that have one
It’s like a key fitting into a end that sits outside the cell
lock. and binds the

Then there’s transduction, ligand, then the snake-like

which means that protein dips in
the receptor protein changes in and out of the cell membrane
some way and seven times,

that activates intracellular and finally ends on the inside

molecules - the of the cell.
second messengers.
The end of the G-protein
The third stage is the cell’s coupled receptor
response to that’s within the cell activates
the signal. intracellular

Zooming into these proteins called guanine

transmembrane receptors, nucleotide-binding
there are three major classes: G proteins or G proteins.
protein coupled
G proteins are made up of
three subunits called
alpha, beta, and gamma, sort of
like a flower
with three petals.
The alpha and the gamma
subunits are anchored
to the cell membrane and keep
the G protein
right next to the receptor.
G proteins bind to guanosine
diphosphate or
GDP when they’re inactive.
When the alpha subunit is
bound to GDP, the
three subunits stay together, so
the flower
is closed.
But when the ligand binds, the
G-protein coupled
receptor changes its shape, and
this allows
the G protein to release GDP
and bind GTP
instead, activating the protein.
When the alpha subunit is
bound to GTP, the
alpha subunit separates from
the beta and
gamma subunits, like one petal
opening and
separating from the others.
When that happens, the alpha
subunit is free
to interact with other proteins -
it stimulates
some while inhibiting others.
But, to act on other proteins,
the alpha subunit
turns GTP into GDP, and when
that happens
the three subunits come
together again - the
flower closes - and the G
protein is turned
off.
Overall, there are three types
of G proteins:
Gq, Gi, and Gs, and each one
stimulates and
inhibits a different set of
enzymes and molecular
pathways.
The Gq protein activates the
enzyme phospholipase
C, which is found in the cell
membrane.
Phospholipase C then cleaves a
phospholipid
called phosphatidylinositol
4,5-bisphosphate
into inositol trisphosphate and
diacylglycerol.
Inositol trisphosphate is
soluble and diffuses
freely through the cytoplasm
and into the
endoplasmic reticulum where
it opens up calcium
channels.
Since the calcium
concentration is higher
in the endoplasmic reticulum
than in the cytoplasm,
calcium flows out of the
endoplasmic reticulum
to the cytoplasm.
The increased calcium
concentration in the
cytoplasm changes the
electrical charge of
the cell and can lead to
depolarization.
Meanwhile, diacylglycerol
remains attached
to the cell membrane and binds
to the enzyme
protein kinase C, which also
relies on calcium
to fully activate.
Once calcium levels in the cell
go up, protein
kinase C starts to activate
proteins by adding
phosphoryl groups to them.
Next is protein Gs which
stimulates the enzyme
adenylate cyclase.
Activated adenylate cyclase
takes adenosine
triphosphate or ATP, and
removes two phosphate
molecules transforming it into
cyclic adenosine
monophosphate or cAMP.
cAMP moves throughout
the cytoplasm and binds to the
enzyme protein
kinase A. Protein kinase A has
two parts - a
regulatory subunit and a
catalytic subunit,
and cAMP specifically binds
the regulatory
subunit of protein kinase A.
When cAMP binds
it makes the regulatory subunit
dissociate
from the catalytic subunit of
protein kinase
A. It’s like pulling the pin out
of the
fire extinguisher allowing it, in
this case
the catalytic subunit, to do its
job.
So after dissociating, the
catalytic subunit
of protein kinase A is free to
phosphorylate
target proteins that trigger a
cellular response.
Finally, there’s the protein Gi,
which is
also bound to adenylate
cyclase - but in this
case, inhibits it, causing
negative feedback
on protein Gs.
This is particularly important
in helping
to inactivate cells.

Next are the enzyme-coupled
receptors.
They’re usually single-pass
transmembrane
proteins, meaning that they
have only one
transmembrane segment, and
their intracellular
end has intrinsic enzyme
activity.
In other words, enzyme-
coupled receptors have
two parts - one domain is the
receptor and
the other domain is an enzyme.
Each domain has a separate
function, like
a swiss army knife composed
of both a knife
and scissors.
The enzymatic domain is
usually a protein
kinase that phosphorylates the
receptor domain.
Now, there are three main
types of enzyme-coupled
receptors, based on the amino
acid the receptors
get phosphorylated at.
The first group are the receptor
tyrosine
kinases.
These are the most common
enzyme-coupled receptors,
and there are many
subfamilies.
Receptor tyrosine kinase are
generally molecules
that can’t phosphorylate their
own tyrosine
side chains.
When a ligand binds, two
receptor chains come
together and dimerize, and
they cross-phosphorylate
one another at multiple
tyrosine residues.
This triggers a conformational
change that
creates high-affinity binding
sites for the
second messengers, which can
also be phosphorylated
and activated, triggering the
signaling pathway.
Next, are the tyrosine kinase
associated receptors
which work in nearly the same
way as receptor
tyrosine kinases, and their
name even sounds
almost the same.
The key difference is that they
have no intrinsic
enzyme activity.
Instead they’re associated with
cytoplasmic
tyrosine kinases.
When the receptors bind their
ligand, the
cytoplasmic tyrosine kinases
phosphorylate
various target proteins to relay
the signal.
Finally, there are the receptor
serine/threonine
kinases and they have a
serine/threonine kinase
domain on their intracellular
end.
There are two classes of these
receptor serine/threonine
kinases - type I and type II -
which are structurally
similar.
Ligand binding brings the two
together together
so that the type II receptor can
phosphorylate
and activate the type I receptor,
which in
turn recruits and
phosphorylates various target
proteins to relay the signal.
Finally, there are the ion
channel receptors
which are generally closed, but
then open
up once they bind a specific
ligand.
They allow ions like chloride,
calcium, sodium,
and potassium to passively
flow down their
gradient.
This leads to a shift in electric
charge distribution
inside the cell, triggering a
cellular response.
Alright, as a quick recap,
autocrine signals
target the same cell, paracrine
signals target
nearby cells, and endocrine
signals target
distant cells.
Hydrophobic ligands are able
to diffuse across
the cell membrane and bind to
receptor proteins
inside the target cell.
Hydrophilic ligands are unable
to cross the
cell membrane, so they must
bind to transmembrane
receptors, which have an
intracellular end
that triggers a signaling
pathway inside the
target cell.
There are three major
transmembrane receptor
classes: G protein coupled
receptors, enzyme-coupled
receptors, and ion channel
receptors.

While there are many different
types of receptors, they can be
broadly classified into cell
surface receptors and
intracellular receptors. This
module will discuss the
structure and function of the
main types of receptors.
A receptor is like a lock, while
the substance binding to it is
the key to that lock. Only
substances keyed to fit the
receptor "lock" can bind to a
particular receptor.
Substances binding to
receptors on cells can tell the
cell to produce a particular
substance (such as a hormone
that makes you feel full after a
big meal), to divide faster
(maybe causing you to add
muscle cells following
exercise) or even to die
(chemotherapy drugs binding
to cancer cell receptors can
signal those cancer cells to
self-destruct).
Cells' receptors are very
specialized and there are in
fact hundreds of different types
of receptors. Most respond to
chemical substances such as
hormones, drugs or allergens,
while some even respond to
pressure or light (your body
produces vitamin D, the
"sunshine hormone," when
sunlight hits your skin).
In some cases, if a cell does
not have the correct receptor
for a particular substance, then
that substance won't affect the
cell.
Leptin is the hormone that
causes you to feel full and
satiated following a big meal.
Cells that don't have receptors
for leptin won't respond to that
hormone, but cells that do have
receptors for leptin will
respond to it, inhibiting the
release of other hormones that
make you want to eat more.
Receptors can play both good
and bad roles in the human
body.
In celiac disease, for example,
receptors on specific immune
system cells serve as the locks
and fragments of the gluten
protein serve as the keys,
triggering celiac's
characteristic intestinal damage
known as villous atrophy.
Certain cellular receptors also
appear to play a role in causing
damage in other autoimmune
diseases. In an autoimmune
disease, your immune system
mistakenly turns on and
damages some of your body's
own cells. Celiac disease is an
autoimmune disease.
But in high blood pressure,
drugs can fit as keys into the
cellular receptors that
otherwise would fit a hormone
that raises blood pressure.
These drugs, known as
angiotensin-blockers because
they block the blood pressure-
raising hormone angiotensin,
can help control your blood
pressure by preventing
angiotensin from signaling
your cells to raise blood
pressure.
Cell Surface Receptors
Cell surface (or
transmembrane) receptors span
the cell membrane and provide
cellular access for ligands that
cannot cross the plasma
membrane themselves. This is
often because these ligands are
hydrophilic or large, making
them unable to diffuse through
the plasma membrane.
There are three main types of
cell surface receptors: ion
channel receptors, G-protein
coupled receptors (GPCRs)
and enzyme-linked receptors.
While these each have unique
structures, cell surface
receptors are generally
composed of three domains: an
extracellular ligand-binding
domain, a hydrophobic domain
embedded within the plasma
membrane, and an intracellular
domain.
 
Ion Channel Receptors
Ion channel receptors are like
gates which open to provide
ions with entry into the cell.
Different subtypes exist, for
example voltage-gated ion
channels, which open or close
in response to changes in
membrane potential. Another
subtype, ligand-gated ion
channels, open or close in
response to the binding of a
specific ligand (for example a
neurotransmitter) to their
extracellular domain. When
they open, they provide a
channel through which ions
can passively enter the cell.
Ion channels are crucial for
many processes, for example
in the nervous system.
Transmission of action
potentials from one neuron to
the next depends on the flow of
sodium and potassium ions via
voltage-gated ion channels.
G-protein Coupled Receptors
GPCRs are a diverse group of
cell surface receptors that use
specific proteins called G
proteins to participate in cell
signaling.
Enzyme-linked Receptors
Enzyme-linked receptors are
cell surface receptors that have
a catalytic site on their
intracellular domain, which is
either associated with an
enzyme or has enzymatic
activity itself, enabling it to
catalyze chemical reactions.
Binding of a ligand to the
extracellular domain leads to
activation of the enzyme and
triggers a specific response. An
important subtype of enzyme-
linked receptors is tyrosine
kinase receptors.
Tyrosine kinase receptors
contain kinase – an enzyme
which transfers phosphate
molecules. In the case of
tyrosine kinase, phosphate
molecules are transferred to the
amino acid tyrosine. When a
ligand binds to the
extracellular domain of a
tyrosine kinase receptor, the
receptor dimerizes with its
neighboring receptor.
Dimerization triggers
phosphorylation of the tyrosine
molecules on the intracellular
domain of the receptor.
Phosphorylated tyrosine
molecules are involved in
many different signaling
cascades which are crucial for
various processes such as cell hormones, and the fat-soluble
division and wound healing. vitamins.
Intracellular Receptors
Intracellular (or internal)
receptors are found inside the
cell, in the cytoplasm or
nucleus. Their ligands tend to
be small, hydrophobic (i.e.
lipid-soluble) molecules,
which can diffuse across the
plasma membrane by
themselves. Once inside the
cell, these ligands bind to their
specific intracellular receptor
to form a ligand-receptor
complex, which will then bind
to DNA in the nucleus and
directly affect gene
transcription and protein
synthesis.
 Like cell surface receptors,
intracellular receptors also
have three core domains.
These comprise a ligand-
binding domain, DNA binding
domain and an amino terminus
(which interacts with the gene
transcription machinery).
Examples of ligands which
bind to intracellular receptors
include sex hormones, thyroid