What are the steps in getting that
signal once it’s bound to the
ligand to do something useful
or do a physiological response?
We have a number of steps
in this signaling process.
We’re going to break them
into six different steps.
The first step is recognition.
You need to make sure that the
ligand binds to the receptor.
So recognition is not
only the first step here,
but it is so important if you
don’t have this response,
you’re not going to get
any of the other steps.
What is that recognition?
The ligand has a specific,
It has a certain charge.
It has a certain way
in which it’s going to
bind in a particular
receptor binding pocket.
Oftentimes, it is very specific to the
ligand itself or class of ligands.
And so, they might have to be one type or a
family to bind to a particular receptor.
We oftentimes talk about that in terms
of its affinity for a receptor.
Certain ligands have high affinities and
other ligands have lower affinities.
It’s important to
understand that reaction
to know what recognition
is going to look like.
Not only do you have to have the
right ligand and the right receptor,
you’re going to have to move that information
from the cell surface into the cell.
How do you do that?
That’s in a stage that we
oftentimes call transduction.
So in a G protein-coupled receptor,
using this as an example,
you might activate a
G protein to help
transduce that signal into
something more useful.
So it is the receptor causing the
change in either the proteins around it
or activating a molecule around
it to start that response.
Transmission is getting that
transduced signal to the right spot.
So it might involve
activating an enzyme
so that then there can be signaling
of the right target proteins.
Once you have the right target proteins
activated, then you get an effect.
And this is what you want
to have happen, right?
You want to either have proteins
being made, enzymes being activated,
genes being up regulated, you might
have proteins being built to sit in the
cytosol or other cell proteins that
might have interesting activities.
But to get to this
you have recognition,
transduction, and transmission.
Once you’ve made this new protein or done
this kind of effect, you get a response.
Now, the response is what we were
usually concerned with in physiology.
So once you’ve made a transport
protein, how does it affect transport?
Once you’ve activated this enzyme, how
has it changed the function of the cell?
Once you’ve up regulated
this gene product,
what happens to not only its
expression but downstream of that?
Interesting though, once you have these
interesting effects that happen,
you’re going to have to eventually
turn the whole process off.
So, you’re going to be have to be able to
terminate this particular cell signaling.
If you don’t terminate the cell signaling,
it will keep going and going and going.
And so, even though you
wanted to amplify the signal
you have to turn it off.
How do you turn it off?
Well, you could either remove the
ligand or block it at some point.
And different cells and different
receptor interactions will utilize
a different process in activating
or terminating the cell signaling.
But you’ll notice that
you’ll have these six steps
in almost all cell-to-cell
Let’s go through a
specific example though
rather than just dealing with
this on a theoretical level.
So if we have an acetylcholine nerve, so
this is a nerve that releases acetylcholine,
it is sent from a neural packet
or quanta of information,
so releases from the presynaptic
traveling across to the receptor
on the postsynaptic membrane.
Acetylcholine will only bind to a
receptor that recognizes it, right?
The type of receptor that’s going to
recognize it is muscarinic receptor.
So acetylcholine has two different types
of receptors, nicotinic and muscarinic.
But if you have a muscarinic receptor
recognizing that acetylcholine
being released, that’s our
first step, is recognition.
The second step is once the receptor
is activated, it needs to do something.
A muscarinic receptor is a G
The G protein-coupled
receptors have these little
G proteins around the
base of the receptor.
There are three different types of
G proteins around this receptor.
The gamma and beta components can then
cleave off and signal something else.
In this case, they’re
transmitting that signal to
somewhere and that part
is a potassium channel.
That potassium channel
will then be activated.
If you activate a
you open it up using the gradient between
the inside the cell and outside the cell,
potassium will leave the cell,
and that is the effector,
is the potassium channel.
The response is a
hyperpolarization of the cell.
That hyperpolarization, if
it’s something like in a
heart cell around an SA
node, will slow heartrate.
So these are the
responses that you get.
You can’t have this response
go on forever, though.
Eventually, you’re going
to have to terminate it.
So how does a muscarinic
receptor terminate the response?
There is an enzyme that
is in the presynaptic
membrane that will break
Acetylcholinesterase will break down
acetylcholine into inactive products,
so then it can no longer bind
to muscarinic receptors.