AP Biology Cellular Communication

Welcome to Educator.com.0000

Today, we are going to be focusing on cellular communication.0002

Multicellular organisms like plants and animals need to coordinate their functions among groups of cells, and they do so by various methods of intercellular communication.0006

Unicellular organisms such as bacteria can also coordinate their functions.0017

For example, they may form a biofilm, and that requires many bacteria working together.0022

We are going to begin by discussing the extracellular matrix.0030

In previous lectures, I reviewed the internal structure of the cell. Now, we are going to talk about the structure outside the cell.0033

The extracellular matrix actually consists of, primarily, a glycoprotein. Glycoproteins, as the name suggests, are proteins, and they have carbohydrate chains attached.0044

In animal cells, the ECM contains primarily collagen fibers.0055

These are a type of glycoprotein, and the collagen fibers are embedded in another type of glycoprotein called proteoglycan.0061

Looking at a cell with its nucleus and various organelles, and then, there is an extra cellular matrix consisting of proteoglycan and collagen embedded within that,0073

collagen fibers embedded in this network, there is also another glycoprotein called fibronectin, and fibronectin provides the connection between the extracellular matrix and integrins.0089

Integrins are proteins on the cell surface. They are cell membrane proteins, and they serve as an intermediary between the cytoskeleton and the extracellular matrix.0113

Here, we have an integrin, and then, fibronectin - let's make that yellow - right here is providing this connection between the ECM and the integrin.0128

Inside the cell, you recall, is a cytoskeleton composed of microtubules, microfilaments, intermediate filaments. It provides structure and support and motility for the cell.0149

And now, you have this integrin connected to the fibronectin and the cytoskeleton and allowing for communication between those two areas.0160

We are going to begin by talking about communication in plants, so intercellular communication in plants.0170

In plants, you may recall that there are channels called plasmodesmata, and these provide a means for communication between the cells0179

because plasmodesmata are channels that actually pass through the cell membrane, through the cell wall, primarily in secondary cell walls and the middle lamella.0188

And the cytoplasm of one plant can communicate directly with the cytoplasm of another.0203

So, substances can be passed from one plant cell to another. Activities can be coordinated this way.0209

Plasmodesmata are an important means of communication among plant cells.0215

Now, let's talk about cell to cell communication in animal cells.0219

Cell junctions are connections between cells, and they allow for communication as well as coordination of activities among these cells.0223

There are three types: desmosomes, tight junctions and gap junctions.0230

First, let's discuss desmosomes. Desmosomes connect adjacent cells through proteins connected to filaments.0235

Each of the adjacent cells will have a desmosome, a desmosomal complex composed of proteins, and these two come together and connect.0248

It is often describe as being like rivets. The cells are essentially riveted together, and intermediate filaments attached to these desmosomal proteins.0258

These are especially common in epithelial cells. Epithelial cells are cells that line surfaces or body cavities such as the respiratory tract or the skin.0272

The skin, for example, is exposed to stressors - wind and rain and sun - and so they need to be held together more tightly.0283

There is actually blistering diseases. One is called pemphigus vulgaris.0292

It is a blistering disease caused by defects in the desmosomal proteins.0296

If there is defects in these proteins, and the cells are not held together, the result can be blisters.0300

The second type of junction is a tight junction. Tight junctions are also often found in epithelial cells particularly in cavities such as the bladder that need to hold fluid0308

because a major function of tight junctions is to prevent leakage of fluids between cells.0325

Tight junctions hold the cells together right flush next to each other at what is called the apical or apical surface of the cell.0336

It is a narrow band that seals - the tight junction is right there - these two cells together.0351

The apical surface, let's say you have a cavity such as the bladder, so if this is the bladder, fluids within the bladder, the side of the cell that is next to the fluid is the apical surface.0364

If there is a whole ring of cells within the apical surface, it would be the urine.0381

And what this tight junction does is it prevents whatever fluid is within the cavity from leaking out between the cells, which is obviously a very important function.0386

The surface that faces away that is not in contact with the fluid, the opposite face, is called the basolateral surface.0395

Again, this is a tight connection between the apical surfaces of cells especially common in epithelial cells.0413

The third type of junction is a gap junction, and we are going to talk about these in more detail when we talk about the neurological system, the nervous system.0421

Gap junctions are actually similar to plasmodesmata in plant cells because these are channels that allow the0434

passage of substances directly from the cytoplasm of one cell to the cytoplasm of the next cell - channels that transport substances0446

from one cell to another, directly from one cell to another, the cytoplasm of one cell to the cytoplasm of another.0468

These often transport ions, and recall that since ions are charged, the transport of them would actually change the membrane potential of the cell.0473

In this way, cells can be coupled electrically and coordinated, and it is actually gap junctions that coordinate the contraction of the heart muscles.0482

Neurons are coupled by synapses, and again, we are going to talk about these in more detail later on in the course.0490

OK, we have talked about various connections between the cells.0499

Now, were going to talk about means of cells signalling, and cells communicate with each other through both electrical signals, so I talked about electrical coupling briefly.0502

They also communicate through chemical signals. For example, substances that are released from one cell can bind to receptors on the target cell.0512

Before we go into depth about that, let's talk about the two general types of signalling.0523

Signalling can occur through direct contact. Signalling can also occur over distances.0529

Plasmodesmata and gap junctions both allow contact through direct communication because substances are transported from the cytoplasm of one cell to the cytoplasm of the other.0543

In plasmodesmata, their cytoplasm are directly communicating, so that is one form of direct contact.0559

A second form of direct contact can be similar to this, but what can happen is one cell has a receptor, and the other cell has plasma membrane proteins that can bind to this receptor.0566

But they do not leave the cell and float over the receptor. Instead, they are actually cell membrane proteins.0585

The cells have to be in direct contact in order for binding to the receptor to occur.0592

Communication through direct contact can be either be through plasmodesmata.0596

It can be through gap junctions, or it can be mediated by receptors and cell membrane proteins that bind to the receptors.0602

Communication over distances occurs via the release of a substance from one cell that, then, binds to the receptor on another cell.0610

Sometimes, the substance that is released is involved in just local signalling, local communication.0621

It is intended for recipients that are nearby cells maybe to coordinate activities between a particular cell type in a tissue.0629

However, communication can occur over much longer distances, and hormones allow that to occur.0636

Hormones are released by cells in glands such as the thyroid gland, the ovaries, the adrenal glands, and they are actually released into the blood stream.0644

Because they are released into the blood stream, they can travel anywhere in the body to the target organs.0661

These cells are shown in close proximity. This would bring more local signalling, but a cell could actually be up in the thyroid.0667

The thyroid releases its hormone thyroxin that can travel through the blood stream and affect organs in different areas of the body.0676

For example thyroxin causes changes in metabolism.0685

It causes increase in temperature, heart rate, blood pressure, many functions throughout the body, and that is mediated by hormones and signalling over a distance.0689

Local regulators only affect nearby cells. Hormones can affect distant target cells.0702

We break cell signalling into three stages. The first stage is reception.0716

The second is transduction, and the third is the response phase; and we are going to go into detail about each of these.0721

First, the reception phase: the reception phase is binding of a ligand to its receptor.0727

This binding induces a conformational change in the receptor. OK, that induces a conformational change, a change in the shape of the receptor protein.0745

Ligands can be neurotransmitters. They can be things like dopamine or norepinephrine.0769

They can be hormones such as insulin.0774

Most ligands are actually water soluble, and the reason why most ligands are water soluble is because the receptors are located on the cell membrane.0776

Since the receptors are on the cell membrane, the ligands bind to those because they cannot enter the cell and just bypass the receptor.0790

Remember that a water soluble molecule is hydrophilic. It is not likely to be able to cross the cell membrane.0797

Again, most ligands are water soluble. Most cannot cross the cell membrane.0804

They bind to the receptors on the surface of the cell.0807

There is a major, very important exception. There are intracellular receptors, and hormones can actually cross the cell membrane and bind intracellularly.0809

I will talk about that again in a few minutes.0819

But for right now, just know that the reception phase is the binding of the ligand to its receptor and that induces a conformational change in the receptor.0821

The second phase is transduction.0829

When we talk about transduction, what we are saying is that the signal is being transduced or transmitted from the cell surface to the inside of the cell,0832

so the transmission of the signal from the cell surface.0841

Norepinephrine or another substance binds to a receptor, and then, that causes a change in the conformation of the receptor, which in turn can activate another protein,0850

which can activate another protein; and that message is passed along to the cell until the final stage.0862

Transduction is just the passing along of the signal, the signals received at the cell surface passed along to deep within the cell,0870

so the transmission of signals from the cell surface to the interior of the cell.0877

The final phase is the response. At last, after the binding and the transduction, the response occurs.0885

The signal that the cell received elicits some type of response. This could be...an example would be transcription of a gene.0896

It could be activation of an enzyme, and activation of an enzyme or transcription of a gene could result in a change in the metabolism of the cell.0911

It could cause the cell to grow. It can even cause a cell to die.0923

The response depends on the particular signal that was received.0926

The signal is received. It is transduced inside the cell and eventually response occurs.0931

To talk about the reception phase, we need to focus on the different types of receptors.0940

There are three major types that you should be familiar with: G protein-coupled receptors, ion channels and receptors with intrinsic enzyme activity such as receptor tyrosine kinases.0944

We are going to talk in this slide about G protein-coupled receptor.0959

Again, three major types you should know. The first is G protein-coupled receptors, and these get their name from the fact that they closely work with a protein called G protein.0962

In blue, this is G protein, and the G protein-coupled receptor is shown on the surface of the cell.0976

Another name for these receptors is seven-transmembrane domain receptors.0985

The reason that they are called seven-transmembrane domain receptors is that their structure is such that they actually have...0995

it is their single polypeptide that has seven alpha helices embedded in the cell membrane.1004

That is where they get this other name that you might hear used.1010

OK, here we have the signalling molecule. It has been released by another cell perhaps, and it is here in the extracellular space.1015

We have the receptor right here in purple and the G protein. What you need to know about G protein is the fact that it exists in two forms.1028

If it is bound to GDP, it is inactive. If it is bound to GTP, it is active.1040

GTP is a form of energy used by the cell. It is similar idea to ATP.1054

Beginning here with stage one, in the first step their receptor is empty. It is unbound, and the signalling molecule is floating around.1062

This G protein is going to be in its inactive form, so it is going to be bound to GDP.1074

Bound to GDP, and it is inactive; and it is located nearby this receptor, the G protein-coupled receptor.1085

The signalling molecule binds to its receptor.1093

And remember that binding of ligand such as the signalling molecule to its receptor, it is a similar idea with specificity between an enzyme and a substrate.1097

When binding occurs, the receptor undergoes a conformational change.1109

This G protein-coupled receptor, the receptor right here, is in a certain from.1116

Binding of the signal molecule causes a change in form that allows the G protein to bind.1123

A conformational change in the receptor - let's say right here - that occurs with binding allows this G protein to bind to the receptor.1132

Binding causes the release of the GDP and from the G protein and instead binding of GTP. The G protein is, now, in its active form.1141

This was stage one. This is stage two.1154

G protein binds to the receptor, releases GDP and binds to GTP. It is now in its active form.1159

Once the G protein is in its active form, it then, is released from the receptor.1170

The receptor has done its job. It lets go of the G protein.1175

The G protein is active. Now, what is this green protein here?1179

Well, this green protein is an enzyme, and it is the next step in the signal.1182

The third stage is that the active G protein is released from the receptor and binds, so GTP bound to the G protein.1191

The active G protein binds to the enzyme, and it, in turn, activates that enzyme.1205

Once that enzyme is activated, it can activate another protein and so on, and then, we get into the transduction step and eventually the response.1212

G protein is also a GTPase meaning that it can hydrolyze the GTP on itself.1223

It is going to go from GTP to GDP putting it back into its inactive form and stopping the cycle.1235

Although, this is a very powerful cycle, it also can be short-lived.1243

Again, going through the steps, the first step is binding of the signalling molecule floating around, empty receptor, receptor attaches.1249

Attachment or binding of the receptor to its ligand results in a conformational change in the receptor.1261

The conformational change allows G protein to bind.1270

When G protein binds to the receptor, it releases GDP and binds GTP, which activates it.1273

The active G protein is released form the receptor and binds to an enzyme. It activates that enzyme.1280

That enzyme, now, can activate another enzyme and so on in the signal transduction cascade.1286

OK, the first type of cell membrane receptor is the G protein-coupled receptor.1293

The second type we are going to talk about is receptor tyrosine kinase sometimes called RTK, and this has what is called intrinsic enzyme activity.1299

Recall that the G protein coupled-receptor underwent a conformational change. It bound to G protein and activated it, but the receptor itself was not an enzyme.1309

Very different with RTK because receptor tyrosine kinases are actually enzymes, and kinases in general, transfer phosphate groups.1320

They actually transfer the terminal phosphate of an ATP, and if you are talking about a protein kinase, then, they are going to transfer the phosphate from ATP to a protein.1340

They transfer the terminal phosphate group from ATP onto the hydroxyl group of a protein.1355

Here, the name tells you what type: tyrosine kinase, so it is going to phosphorylate tyrosine.1362

There can be serine kinases, various types of kinases that specifically phosphorylate certain amino acids on protein.1367

OK, this receptor is a tyrosine kinase. It has the ability to phosphorylate tyrosine, and, in this case, it actually performs autophosphorylation.1377

That means that it phosphorylates itself. It phosphorylates tyrosines on its own protein.1391

This receptor exists in two forms. The first form is monomer.1417

You see, there is a single structure, a single receptor, and that is in inactive form; and you see that right now, it is not bound to a ligand.1422

Upon binding of the signalling molecule to the receptor, two of these monomers come together to form what is called a dimer.1434

They undergo dimerization, and the dimer form is the active form.1444

Once in their active form, then they can perform the phosphorylation.1453

The structure of this is that there is a helix embedded in the cell membrane, and there are multiple tyrosines on this protein.1458

These are unphosphorylated, and then, once the RTK is in its dimer form, it is activated, and it can phosphorylate itself.1474

It is going to add phosphate groups, and it is going to use ATP, so 4 ATPs will be converted to 4 ADPs to provide the phosphates.1486

This phosphorylated form of RTK is recognized by proteins within the cells.1500

These particular proteins do not recognize the unphosphorylated form, but once it is phosphorylated,1506

then, certain intracellular proteins will bind to the receptor molecule and different proteins can bind.1512

There are several different ones that will bind, and each of these could start a different signalling cascade.1530

That might be one cascade, and then, there are may be a different cascade over here.1539

And this is very important because this one receptor can trigger multiple responses by the cell, and this is very helpful to coordinate cell functions for example growth.1545

For growth to occur, organelles need to be duplicated. More plasma membrane needs to occur replication of DNA.1556

In order to coordinate multiple processes within the cell, that is made much easier by the fact that several cascades can be started just by the binding in the signal molecule.1564

Again, there are two forms. There is the inactive monomer form and the active dimer form.1580

Binding of the ligand to the receptor tyrosine kinase receptor triggers dimerization.1585

Once RTK is in its active form, it can phosphorylate itself, the tyrosine, amino acids, on itself, and that puts the protein into a form that is recognized by proteins within the cell.1592

These proteins bind. Those proteins are activated, and they will activate downstream proteins again, starting that signal transduction cascade.1605

And multiple cascades can be started by the various different proteins that bind.1615

The third type of receptor that we are going to talk about are ligand-gated ion channels.1623

These function differently than the other types that we discussed.1628

These open upon binding to a specific molecule, and they are called gated channels because they open, and they close much like a gate.1631

They exist in two forms.1642

Here is the channel, and in its closed form, molecules cannot get in.1644

In its open form like this, a particular ion such as calcium can enter the cell.1654

These are called ligand-gated, meaning that it is a ligand that opens the gate, bind the receptors.1664

They bind ligands, and in this case, when a signalling molecule comes along - let's say that this is a signalling molecule, and we will say that these are calcium ions - it binds.1670

Binding is going to induce this gate to open.1686

The gate is, now, over here. It is no longer blocking the channel.1702

Once this channel is opened, calcium ions can enter the cell.1707

Eventually, this signalling molecule will dissociate from the receptors.1716

The signalling molecule is still bound here because the gate is open.1720

Again, channel was closed, signalling molecule bound, induces a conformational change that opens up the gate, calcium molecules can enter the cell.1728

And then, this is going to eventually dissociate, so it is going to float away.1740

And now, the gate is going to be closed again, and no more calcium ions can enter, so the signal will be shut off.1747

Once calcium enters the cell, that can trigger a response from the cell or a cascade similar to what we talked about earlier on.1756

We are going to talk about these in detail when we discuss the nervous system because the influx of calcium channels are important for the nervous system.1766

They are important for contraction of muscles and transmitting signals throughout cells.1774

The receptors that I have been talking about, so far, were all located on the cell membrane.1785

We talked about G protein coupled-receptors, receptor tyrosine kinase, channels in the cell membrane, ion channels in the cell membrane.1789

However, there are also intracellular receptors.1799

With the receptors we have talked about previously, the ligands were water soluble.1803

They were hydrophilic. They cannot easily enter the cell, so instead, they would bind to the receptors on the surface of the cell.1809

They cannot bypass the receptors. However, hydrophobic molecules such as hormones may have intracellular receptors.1815

Here, we have a receptor.1827

Steroid hormones can enter the cell because they are hydrophobic.1834

Similar idea to what we discussed earlier in that there is specificity, so here is a hormone, recall that hormones are released from glands.1842

They can travel through the bloodstream to the distant target organs. Initially, they are located outside of the cell.1853

They can cross the cell membrane and then bind to the receptor.1860

This forms what is called a receptor ligand complex. This receptor ligand complex can travel into the nucleus of the cell because, again, it can cross cell membranes.1864

Once it is inside the nucleus, it can act on DNA. It can act as a transcription factor and activate transcription of messenger RNA, or it can actually turn off transcription.1884

In this case, you notice that there is no intermediate step of transduction.1896

The receptor binds to the hormone, and this complex directly causes the response.1900

Rather than having binding to receptor tyrosine kinase and then, activating another protein, which activates another protein and so on until the response,1905

here, we just have binding of the hormone to the receptor, which directly acts as a transcription factor.1917

Here, it says intracellular receptors are located in the cytoplasm or in the nucleus.1927

What is shown here is an example of a receptor in the cytoplasm, binds to its molecule, signal molecule enters the nucleus.1931

However in some cells, the receptor is located in the nucleus, so the receptors in the nucleus, and the signal molecule will enter the cell, travel to the nucleus, and then bind there.1939

Again, receptor ligand complex can go ahead and act as a transcription factor, and it is already in the nucleus ready to do so.1959

A typical hormone that would act in this way is thyroid hormone.1966

Thyroxin, the hormone released by the thyroid gland binds to a receptor that is located in the nucleus of the cell.1970

We talked about the first phase, the reception phase.1980

We also started talking about signal transduction, and now, we are going to continue on in more detail to investigate that phase of cell signalling.1982

The first phase was reception.1992

This signalling molecule binds to the receptor, and we are talking mainly about receptors that are on the surface of the cell membrane, so binds to the receptor.1995

The receptor undergoes a conformational change, and that change triggers, activates another protein,2006

which activates another protein and creates what is called a signal pathway, signal transduction pathway or a cascade.2012

Sometimes it is called a signal cascade because its one activation causes the next causes the next. It is a cascade effect.2020

These pathways often use what is called a second messenger such as cyclic AMP.2030

These are small molecules that help to transmit the message from the surface of the cell to within the cell.2035

Other second messengers could be calcium, could be IP3 and diacylglycerol, DAG, and we are going to talk about each of these.2043

Over here is the structure of cyclic AMP, and this is an important second messenger, so we are going to cover this right now.2054

The first messenger...so, there is a second messenger. What is the first messenger?2061

The first messenger is the signalling molecule. It brings the message to the cell from elsewhere in the body - binding of norepinephrine or internally binding of a hormone.2064

That is the first messenger. It brings the signal.2080

The second messenger carries that signal through the cell, helps carry it through the cell, until eventually, the response is elicited.2083

G protein-coupled receptors used second messengers - I am going to use these as an example.2093

Just briefly revealing how G protein-coupled receptors work, I am showing a G protein-coupled receptor here already bound to its signal molecule.2099

Since it is bound to its signal molecule, it will undergo a conformational change that allows the nearby G protein to bind to it.2111

When G protein binds to the G protein-coupled receptor, it releases GDP and binds to GTP.2125

That puts it in its active form.2135

Recall that once the G protein is in its active form, it is actually released from the receptor, and it activates another protein.2139

Now, we are going to talk about what that other protein is.2153

Located near the G protein is an enzyme called adenylyl cyclase, and what adenylyl cyclase does is it catalyzes the production of cyclic AMP.2156

It converts ATP to cyclic AMP - shown here - which is a second messenger.2178

The binding of this active G protein to adenylyl cyclase activates it. The result is going to be the production of cyclic AMP.2194

Levels of cyclic AMP in the cell are going to be greatly elevated, lots more of these floating around in the cell.2205

Again, activation of the G protein by binding to its receptor, active G protein dissociates from the receptor and binds to the enzyme adenylyl cyclase.2215

Adenylyl cyclase raises the level of cyclic AMP in the cell by catalyzing the transformation of ATP into cyclic AMP.2226

Cyclic AMP can, then, in turn activate other molecules. We have the cyclic AMP that could bind to another protein, for example a protein kinase.2240

Then, this protein kinase might go and phosphorylate another protein, which is often a kinase, and once it phosphorylates that kinase, it might activate it.2253

And then, that protein will activate another protein, and sometimes you will see these type of phosphorylation cascades,2268

where one protein kinase activates another, which activates another; and that continues on.2274

Phosphodiesterase is an enzyme that catalyzes the reaction, where cyclic AMP is changed to just AMP.2283

That will actually deactivate the cyclic AMP, and it will just become AMP; and that will stop this cascade.2302

This cascade is powerful, again, but short-lived because the cyclic AMP level is going to quickly rise once adenylyl cyclase is activated.2310

But then, once phosphodiesterase converts cyclic AMP to AMP, then, there is no longer enough cyclic AMP around2320

to activate this phosphorylation cascade or whatever enzymes are downstream, and so the process stops.2329

Again, the idea with the second messenger is that it is a small molecule such as cyclic AMP2337

that helps to transmit the signal from the cell surface inside the cell, and it does that by activating a protein.2342

Cyclic AMP can also be a second messenger for cascades involving receptor tyrosine kinase.2350

Signal transduction pathways often involve more than one second messenger.2361

In the previous slide, I focused on cyclic AMP, other second messengers, cyclic GMP. I also mentioned calcium ions as well as IP3 and diacylglycerols.2365

Let's focus on some of those, so calcium, IP3 and diacylglycerol or DAG.2382

Again, we are going to talk about G protein-coupled receptor starting out at the step at which the receptor binds to the G protein and activates it.2392

Here is a different enzyme this time. Instead of the active form of the G protein, it is going to dissociate, now, I have got active form of the G protein.2407

Instead of binding to adenylyl cyclase, in this cycle, it is going to activate a different enzyme, and this enzyme is called phospholipase C.2421

Phospholipase C is located right near the cell membrane, and the reason is because its job is to cleave a particular type of phospholipids into DAG and IP3.2436

IP3 and DAG come from cleavage of phospholipids in the cell membrane.2448

Phospholipase C cleaves a particular type of phospholipid called PIP₂ into IP3 and DAG.2454

Again, form follows function, so I would expect phospholipase C to be located near the G protein,2473

which activates it and also next to the cell membrane, so it can cleave phospholipids within the cell membrane.2478

Active G protein is going to go over and bind and activate phospholipase C. Phospholipase C is, then, going to create IP3 and DAG.2486

IP3, then, acts as a second messenger by going over to the endoplasmic reticulum and binding to a ligand-gated calcium channel. This is a ligand-gated calcium channel.2512

Recall that in the ligand-gated calcium channel the gate is closed until a particular molecule binds.2536

In this case, the ligand that needs to bind is IP3, so the IP3 comes over here and binds.2543

The result is release of calcium into the cytoplasm greatly increasing levels of calcium in the cell.2548

Calcium, then, continues on and activates other enzymes. It continues on with the signalling pathway.2556

Meanwhile, DAG can activate a separate pathway.2564

As you see, it can be quite complex when multiple second messengers are involved.2570

Again, the starting point was binding of the signalling molecule and activation or a conformational change on the receptor that activates G protein.2575

Active G protein activates the enzyme phospholipase C.2586

Active phospholipase C catalyzes the transformation of phospholipids in the membrane into two second messengers. One is IP3; the other is DAG.2590

DAG, we had PIP₂, and it was cleaved2601

It is within the cell membrane. It was cleaved into these two.2608

DAG can go off and activate other proteins, for example maybe a protein kinase, and that could start a chain of reactions to create a response within the cell.2611

Meanwhile, IP3 can go over and bind to the ligand-gated calcium channels in the endoplasmic reticulum.2621

That is going to release calcium, and that is going to go ahead and continue the response.2628

One thing to note here, when we talked about cyclic AMP, the level of cyclic AMP was increased by adenylyl cyclase catalyzing the reaction of ATP being converted into cyclic AMP.2635

It was actually the creation of cyclic AMP.2648

Here, the second messenger calcium, the level was increased, but it was not through creation of calcium.2650

It was just through the release of stored calcium from the endoplasmic reticulum. That is a different mechanism to increase the level of a second messenger.2656

What is very important about signal transduction pathways is also that they can amplify a signal.2667

Binding of one signal molecule allows the receptor to activate this G protein. The G protein can activate phospholipase C.2676

Phospholipase C can, then, create multiple molecules of IP3.2688

The binding of just the one signal molecule can activate enzymes that can catalyze the reactions many times, create many second messenger molecules.2694

All of those IP3s can, then, go on and open the channel. All of the DAGs can go trigger a pathway, so at each step the signal can be amplified.2705

OK, it started out with binding of the receptor by a signal molecule.2716

The message is transduced through the cell, finally reaches inside the cell, and you get the response.2722

The whole point of the binding was to trigger some, sort of, response by the cell.2728

When we talked about intracellular receptors, that happened in a very direct fashion. The receptor is in the cytoplasm or maybe even in the nucleus.2733

It is right there. It can act directly in the DNA as a transcription factor without all the intermediary steps.2741

Even if there are intermediary steps, the result is still a response by the cell.2748

What are the types of responses?2753

I also mentioned increasing or decreasing transcription of a gene.2755

If the cell is going to grow, and it needs to make certain proteins, then it can turn the genes for that protein on. Messenger RNA is transcribed.2761

It is transported to the cytoplasm. It is translated into a protein, and there are increased levels of a protein.2772

The response can be increasing or decreasing transcription, which, ultimately, makes more of a protein, or you will have less of a protein.2778

However, there is a second way in which the cell can respond. It can act upon a protein that already exists.2786

Sometimes, the pathway does not cause more or less protein to be produced. Instead, it works on a protein that exists and makes it more or less active.2793

That change in protein activity can result in changes in the metabolism of the cell, the shape of the cell, the growth of the cell. It can even result in cell death.2807

You should be familiar with apoptosis. This is known as programmed cell death, and it is one outcome of binding of certain signal molecules to receptor.2817

Programmed cell death has a very distinctive look. It is different than death of a cell just by outside destruction.2830

In order for growth and renewal, apoptosis has to occur.2838

First of all, of course, damaged cells need to be eliminated, so if a cell has been infected by a virus, or the DNA is seriously damaged, that may trigger this signal for apoptosis to occur.2843

Apoptosis is also a part of development. It is a part of embryological development.2856

For example, cells are pruned back in the nervous system. They are also pruned back between the fingers and the toes so that those do not end up webbed when were born.2860

Apoptosis is an important part of an organism, and it can be triggered by binding of a signal molecule.2869

It has a very distinctive appearance. What happens is the DNA fragments, the cell shrinks, and it forms these what are called "blebs" on its surface.2877

You might hear this called cell suicidal, so it is programmed cell death.2894

End results of binding of a signal molecule can be growth of the cell, increase in metabolism.2898

It could be release of a certain substance by the cell, or it could be even the death of the cell.2905

Example one: describe the structure of tight junctions and gap junctions.2911

OK, cells with tight junctions are close together. They are flushed next to each other.2916

They are...adjacent cells will be very close together, and they are held in placed by proteins near the apical surface,2922

adjacent cells held close together by proteins, by band of proteins near the apical surface.2930

Again, the apical surface is the surface that is going to be near the interior of a cavity or the lumen of a cavity.2945

The apical surface is going to be on this side, and the basolateral surface is going to be the other side of the cell near apical surface.2954

Gap junctions, first, this is tight junctions, Gap junctions are protein channels that allow the cells to pass substances directly from the cytoplasm of one cell to the cytoplasm of the other.2965

These are channels between cells, and they allow the transport of substances from the cytoplasm of one cell directly into the cytoplasm of the other.2982

How do these differing structures reflect the functions of these two type of intercellular connections?3001

Well, if you think about tight junctions, one function they have is to prevent the leakage of fluids.3009

And this structure reflects that because the side of the cell that is the apical side is going to be the side that is next to the liquid.3020

If there is liquid in here, you can prevent the leakage of fluids from between the cells by having them pressed next to each other.3032

Otherwise, the fluid would just leak out, and then, the cavity would not be very effective.3041

Instead, with the tight junctions, the fluid is held into the space that it needs to be in.3049

This also controls the passages of substances. Substances cannot just pass through here.3055

The only substances that can get through are ones that the cell allows to cross, so that is tight junctions.3059

Gap junctions have different functions. One function of gap junctions is electrical coupling.3065

Electrical coupling is the coordination of charge between cells, and this occurs on the nervous system. It also allows the heart to beat in a coordinated manner.3074

Electrical coupling occurs when ions pass from cell to cell since they are charged, and they can pass that electrical signal along.3084

Ions pass from cell to cell, and this occurs through gap junctions, so the structure of channels allows for that coordination.3094

Describe the three phases of cell signalling.3109

The first phase is the reception phase. The second phase is transduction, and the third phase is response.3112

In the reception phase, the signalling molecule binds to the receptor and induces a conformational change in the receptor, which activates the receptor protein.3129

That is the reception phase.3165

In transduction phase, the signal is transmitted from the cell surface to the interior of the cell.3166

This, often, is mediated by a cascade, in which the receptor activates a protein, which in turn activates another protein and on to the cell, and these proteins may be enzymes.3186

Transduction is often mediated by small molecules called second messengers such as cyclic AMP, calcium, IP3.3198

The third phase is the response phase. The message is finally received by its final recipient.3206

A response could be enzyme is activated and increase or decrease of transcription.3214

It could be growth or death of the cell. It could be a release of a substance.3228

The response phase is the cell reacting to that binding of the signal molecule.3235

The signal has been received. The cell reacts accordingly.3240

Why are ligands for intracellular receptors either hydrophobic or very small?3245

Ligands for intracellular receptors, these ligands, these type of ligands must cross the cell membrane to reach their receptors.3254

Their receptors are located either in the cytoplasm or in the nucleus of the cell.3269

Recall that molecules that can cross the cell membrane are small. They are non-polar, and they are not charged; or they are polar, but they are very small.3275

In general though, a small hydrophobic molecule will be best equipped to cross the cell membrane.3290

Steroid hormones meet the criteria of easily crossing the cell membrane, so they can bind to the receptor within the cell.3297

What is the cell's eventual response to the binding of a hormone to its intracellular receptor? What is the mechanism by which this occurs?3305

When a hormone binds to a receptor inside the cell, a hormone - actually a receptor, let's just say receptor- ligand complex is formed.3316

This is either already in the nucleus - if the receptor is in the nucleus - or it is in the cytoplasm, and it travels to the nucleus.3324

I am going to say "travels to nucleus". It may already be in there and activates or supresses transcription.3342

The effect will be an increase in the messenger RNA or decrease and then, eventually an increase or decrease in the level of a particular protein.3355

Example four: how does signal transduction amplify the response of a cell to the binding of a molecule to a receptor?3368

One receptor can activate many proteins. The receptor is bound by one signal molecule, but that receptor can activate many proteins.3378

Each of those can activate many proteins, or if it is an enzyme, maybe act on many substrates. Therefore, at each step, the signal is amplified.3392

You start out with just one binding molecule, but maybe the receptor activates ten proteins. Each of those ten proteins can activate ten more and so on.3412

It gets amplified at each step, which is very important to the cell's functioning and very efficient.3423