Cell Communication

Importance of Cell Communication

Multicellular organisms (such as yourself, of course) are incredibly complex. As a result, a lot of coordination is necessary. Coordinating amongst cells is just like coordinating amongst humans. Cells need to communicate. Think about a busy intersection - there are a lot of independent parts moving. These parts are analogous so cells in a multicellular organism. The cars, like cells, all have different kinds of things happening within them - some have kids screaming, some drivers are eating, etc. but these cars have to interact and coordinate. If not, there will be utter mayhem - cars will run into each other constantly, traffic will be halted, and much worse.

You may not think about how you communicate with these other drivers because it is so natural for us. Turn signals, brake lights, eye contact, hand signaling, nodding, waving, obeying traffic lights, and even bumper stickers are all examples by which cars in an intersection might communicate. Cells have their own forms of communication, of course - typically involving signaling molecules that move between and within cells.

Obviously, cells are not exactly like cars, but cells still need to communicate in order to keep the whole multicellular organism alive and well. Think about it this way - your stomach needs food to do its job properly, but the stomach has no way by which to get food. So, the stomach must outsource that job to the mouth. You can't request help if you cannot communicate!

Types of Signaling

In reality, there are multiple ways by which cells might communicate with one another. However, the scope of this course only focuses on chemical signaling. Chemical signaling is simply communication between cells that involves some other particle or molecule as a messenger. This message will be sent by a cell in one area and that message will be received at another cell (or sometimes even in a different place within the first cell).

Remember, these signals are all molecules (ligands), so they typically will bind to a specific place (receptor) in or on the surface of the target cell. Some signaling molecules can enter the target cell (small, nonpolar - remember cell membrane permeability?) and others must bind to a specific receptor for that ligand.

Signal Transduction Pathways

When a signaling molecule is received by a receptor in the target cell, it will trigger a response, of course. After all, what would be the point of communicating if no action was taken? That response can be wildly different depending on the signal involved - it may trigger an increase in gene expression of a particular gene or it may trigger apoptosis (programmed cell death) in the cell. Whatever the intended response may be, a received signal is the beginning of a pathway, one that will take our signal's information and stimulate a response in a target cell. This pathway is known as a signal transduction pathway, or a series of steps from signal reception to cell response.

A signal transduction pathway can be boiled down to three major steps: reception, transduction, and response. In reality, these steps can be more complex than shown in this simplified diagram, but it is only the understanding of these three steps that you must know, not any specific molecules.

Signals or Ligands

Signals (ligands) start the process of reception- however, if the signal is a lipid it can go right through the cell membrane and bind to a receptor inside the cell. Ions and proteins must bind to a cell membrane surface receptor. Note: some hormones are lipids (steroids) like estrogen and testosterone while other hormones are proteins like insulin.

1.Reception

In the reception stage, the signaling molecule (which likely came from another cell) is received by a receptor (hence the name reception). This is nothing new to you because you have seen molecules bind to enzymes countless times by now!

This binding of the ligand, of course, stimulates a conformational, or shape, change in the enzyme. This change ultimately triggers the next stage of the pathway: the transduction stage.

2. Transduction

Transduction, the second step in a signal transduction pathway, is all about passing that message along to whoever needs to hear it. The information is passed between relay molecules (just like a baton in a relay race) and eventually will be moved on to the final step. Transduction typically involved many different proteins, but sometimes involves just a short series of steps as shown in this simplified diagram.

3. Response

When the information finally reaches the end of the transduction step, it is time for the cellular response. The cellular response is what this has all been for. Whatever is needed in response to that signaling molecule occurs here - it could be an alteration of gene expression, an immune response, or virtually anything else.

The cellular response's location will differ depending on what the response is. If the response involves the DNA, then the response will occur (or at least begin) in the nucleus where the DNA is housed (in eukaryotes). If the response involves an organelle such as a lysosome, then it will occur at that organelle, of course. You do not need to memorize any particular cell responses for any specific pathways, but some you will see as examples will be useful to keep in mind in case you are shown something similar on an exam.

Forms of Signaling

There are four categories of chemical signaling found in multicellular organisms: paracrine signaling, endocrine signaling, autocrine signaling, and direct signaling across gap junctions ( The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell. Not all cells are affected by the same signals.

Fig: In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by gap junctions, a nearby cell (paracrine signaling), or a distant cell (endocrine signaling). Paracrine signaling acts on nearby cells, endocrine signaling uses the circulatory system to transport ligands, and autocrine signaling acts on the signaling cell. Signaling via gap junctions involves signaling molecules moving directly between adjacent cells.

1.Autocrine

In autocrine signaling, a cell signals to itself, releasing a ligand that binds to receptors on its own surface (or, depending on the type of signal, to receptors inside of the cell). This may seem like an odd thing for a cell to do, but autocrine signaling plays an important role in many processes.

For instance, autocrine signaling is important during development, helping cells take on and reinforce their correct identities. From a medical standpoint, autocrine signaling is important in cancer and is thought to play a key role in metastasis (the spread of cancer from its original site to other parts of the body)

Apoptosis - a special autocrine signal

Apoptosis is when a cell receives a signal from itself to destroy itself.

It can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors

Apoptosis is also important in the development of digits, by killing certain cells

2. Juxtacrine

Also called Cell -to- Cell Contact

either through:

a. gap junctions or in plants it is known as plasmodesmata

b. Cell-to-Cell Recognition (we see this with viruses and immune cells)

3.Paracrine

Often, cells that are near one another communicate through the release of chemical messengers (ligands that can diffuse through the space between the cells). This type of signaling, in which cells communicate over relatively short distances, is known as paracrine signaling.

Paracrine signaling allows cells to locally coordinate activities with their neighbors. Although they're used in many different tissues and contexts, paracrine signals are especially important during development, when they allow one group of cells to tell a neighboring group of cells what cellular identity to take on

3. a. Synaptic Signaling

Synaptic signaling

One unique example of paracrine signaling is synaptic signaling, in which nerve cells transmit signals. This process is named for the synapse, the junction between two nerve cells where signal transmission occurs.

When the sending neuron fires, an electrical impulse moves rapidly through the cell, traveling down a long, fiber-like extension called an axon. When the impulse reaches the synapse, it triggers the release of ligands called neurotransmitters, which quickly cross the small gap between the nerve cells. When the neurotransmitters arrive at the receiving cell, they bind to receptors and cause a chemical change inside of the cell (often, opening ion channels and changing the electrical potential across the membrane)

4. Endocrine

When cells need to transmit signals over long distances, they often use the circulatory system as a distribution network for the messages they send. In long-distance endocrine signaling, signals are produced by specialized cells and released into the bloodstream, which carries them to target cells in distant parts of the body. Signals that are produced in one part of the body and travel through the circulation to reach far-away targets are known as hormones.

In humans, endocrine glands that release hormones include the thyroid, the hypothalamus, and the pituitary, as well as the gonads (testes and ovaries) and the pancreas. Each endocrine gland releases one or more types of hormones, many of which are master regulators of development and physiology.

For example, the pituitary releases growth hormone (GH), which promotes growth, particularly of the skeleton and cartilage. Like most hormones, GH affects many different types of cells throughout the body. However, cartilage cells provide one example of how GH functions: it binds to receptors on the surface of these cells and encourages them to divide

Internal receptors

Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane

Cell-Surface Receptors

Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Because cell-surface receptor proteins are fundamental to normal cell functioning, it should come as no surprise that a malfunction in any one of these proteins could have severe consequences. Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer.

There are a couple of important types of receptors to understand

1. G Coupled Receptors

G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane (Figure). All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own specific extracellular domain and G-protein-binding site.

Cell signaling using G-protein-linked receptors occurs as a cyclic series of events. Before the ligand binds, the inactive G-protein can bind to a newly revealed site on the receptor specific for its binding. Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which releases GDP and picks up GTP. The subunits of the G-protein then split into the α subunit and the βγ subunit. One or both of these G-protein fragments may be able to activate other proteins as a result. After awhile, the GTP on the active α subunit of the G-protein is hydrolyzed to GDP and the βγ subunit is deactivated. The subunits reassociate to form the inactive G-protein and the cycle begins anew.

Cholera is a perfect example of a disease caused by G coupled Signal Pathway Disruption

2. Enzyme-linked receptors

are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. The enzyme-linked receptors normally have large extracellular and intracellular domains, but the membrane-spanning region consists of a single alpha-helical region of the peptide strand. When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response. One example of this type of enzyme-linked receptor is the tyrosine kinase receptor (Figure). A kinase is an enzyme that transfers phosphate groups from ATP to another protein. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules (tyrosine residues). First, signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors. The two neighboring receptors then bond together, or dimerize. Phosphates are then added to tyrosine residues on the intracellular domain of the receptors (phosphorylation). The phosphorylated residues can then transmit the signal to the next messenger within the cytoplasm.

3. Ion channel-linked receptors

Receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. In order to interact with the phospholipid fatty acid tails that form the center of the plasma membrane, many of the amino acids in the membrane-spanning region are hydrophobic in nature. Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for the passage of water or ions. When a ligand binds to the extracellular region of the channel, there is a conformational change in the protein's structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through

Quorum- Sensing- Bacteria Communication

Quorum-sensing allows individual bacteria within colonies to signal each other to coordinate and carry out colony-wide functions such as sporulation, bioluminescence, virulence, conjugation, competence, and biofilm formation

Copy of Cell Communication and Cell Cycle

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