Cell Bio Chapter 16

Cell Signaling

Cell signaling is

The process where cells with the same genetic information receives and transmits messages from itself, other cells, or the environment

Everything needed in cell signaling cascade step by step

Signaling molecule (Ligand) > receptor protein > chain of signaling molecules activated > activates effector proteins > each effector protein carries out cell response

How the cell signaling cascade works - in depth

The ligand (signaling molecule) attaches to the receptor protein.

This receives information which in turn activates the receptor protein

This will trigger a chain reaction of post-translational modifications through the chain of signaling molecules in the cytoplasm

Each will be activated and turned on and will pass the signal to the next protein and turned off after the signal passes through them- an example could be through phosphorylation dephosphorylation

The last activated signaling molecule will activate all of the effector proteins. There are different types of effector proteins that activate different cell responses in different parts of the cell. Will carry out the final cellular response

ex) altering gene expression in the nucleus, changing metabolism in enzymes, changing shape or movement in cytoskeleton

What are the 4 major types of cell signaling?

Endocrine - long-distance signaling

Paracrine - localized signaling

Neuronal - electrical signaling

Contact-dependent - direct physical contact

What are the 4 major types of cell signaling classified off of?

The distance that the signal molecule travels

Explain endocrine signaling

Long-distance hormonal signaling. An endocrine cell releases a signaling molecule (hormones) are released into the bloodstream to reach target cells throughout the entire body

Example of endocrine (hormonal) signaling

Seggs hormones: Estrogen, progesterone, Testosterone, Cortisol

Estrogen and Progesterone are produced in the ovaries

Testosterone is produced in the testes

Cortisol is produced by the adrenal glands

Once secreted into the bloodstream, these hormones travel throughout the body. Face - facial hair, chest - breasts, brain - mood

Explain paracrine signaling

Localized signaling within 1 tissue or organ. These signaling molecules do not go into the bloodstream. They reach the nearby target cells

Examples where paracrine signaling can take place

Just the heart, eyes, 1 tissue

Explain contact-dependent signaling

The signaling molecule and the receptor molecule are membrane-bound on two different cells. Therefore, the 2 cells have to be touching one another for the signal to pass. Can have one cell in the middle of a circle of surrounding cells, passing a signal to each of them. The receptors and the signaling molecules have to physically touch

Does the receptor and signaling molecule physically touch in endocrine, paracrine, or neuronal signaling?

Yes, they always have to touch, but the difference is how far the signaling molecule has to travel to reach the receptor molecule

Example of contact-dependent cell signaling

Notch-Delta signaling in the development of a fly’s nervous system

Each cell has both the Delta protein (signaling molecule) and the Notch protein (receptor molecule) on its membrane.

For signaling to occur, the Delta protein on one cell has to directly touch the Notch protein on another cell - Both cells have to physically touch

Determine the future neurons or skin cells for the fly

Explain Neuronal cell signaling

This is local, electrical signaling. An electrical impulse shoots through a neuron and releases neurotransmitters which are chemical signaling molecules. The neurotransmitters physically touch to the receptor cell (muscle cell or neuron)

This happens super fast

Give an example of how one chemical signal can produce completely different responses depending on the cell type it interacts with

Acetylcholine - a signaling molecule. Different types of acetylcholine receptors on different cell types react to acetylcholine differently

Give the ways acetylcholine creates different responses based on the different cells it interacts with - Skeletal muscle cells

Acetylcholine binds to its receptors on the cell membrane and causes the muscles to slide together and contract

Give the ways acetylcholine creates different responses based on the different cells it interacts with - Heart pacemaker cells

When acetylcholine binds to its receptors on the cell membrane, the cells become very negative, which decreases the heart rate by reducing the strength of the contraction

Give the ways acetylcholine creates different responses based on the different cells it interacts with - Salivary Gland cells

When acetylcholine binds to its receptors on the cell membrane, the cells release saliva into the mouth, causing secretion

What are there different signals for?

Survival factors, Grow and divide factors, differentiate factors

What does the absence of cell signals cause for a cell?

Undergo apoptosis - programmed cell death

What is the cell type that is an exception to cell signals and can continue to live without them?

Cancer cells. They keep dividing and don’t need any signals to grow

What type of responses exist once the receptor protein obtains a signaling molecule?

Fast cascades and slow cascades - How quickly a cell responds to an outside signal

What do fast cascades and slow cascades depend on?

Speed depends entirely on whether the cell can use pre-existing proteins (fast) or if it has to make brand new proteins from scratch (slow)

Fast cascades

The signal turns on/off proteins that already exist through post-translational modifications. Temporarily alters activity. Does not need to go to the nucleus

Examples of fast cascades

Phosphorylation dephosphorylation

GTP Binding

Quaternary Regulation

Slow cascades

The signal must alter gene expression by traveling into the nucleus. This builds entirely new proteins from scratch. It targets the transcription regulatory protein (a type of effector protein). Permanently alters cells into new types of cells.

What are intracellular cell receptors?

Receptor proteins that are inside the cell (either in the cytoplasm or the nucleus). The ligand (signaling molecule) has to be small and hydrophobic (no charge) in order to get through the hydrophobic cell membrane and reach the receptor

What are cell surface receptors? (transmembrane)

Embedded directly within the plasma membrane, with a portion of it facing the environment. The signal molecule is hydrophilic, since it cannot move through the hydrophobic membrane.

Examples of hydrophobic hormones

Sex hormones - estrogen, progesterone, and testosterone

Stress hormone - Cortisol

What are hydrophobic hormones?

Hydrophobic hormones are a type of signaling molecule where its receptor protein is inside of the cell. Therefore, these hormones must be small and hydrophobic in order to get through the membrane.

Which hydrophobic hormones are slow cascades?

Cortisol (stress hormone) because it has to enter the nucleus and alter DNA expression

But sex hormones can also be slow cascaces depending on its pathway (example: pubertal development)

Which hydrophobic hormones are fast cascades?

Primarily sex hormones. Have cell surface receptors. Speed depends on pathway (quick behavioral shifts)

What is a classic example of paracrine signaling? What type of cell?

Endothelial cell.

Explain paracrine signaling involving endothelial cells

The release of nitric oxide controls the widening of blood vessels

Only within the blood vessel wall - tissue

Endothelial cells under stress activate an enzyme that releases Nitric Oxide gas (the ligand) inside the cell - NO is hydrophobic

The gas travels through the endothelial cell membrane and crosses the space between the cells to go inside the smooth muscle (intracellular receptor)

NO binds to the receptor inside smooth muscle cell and starts the chemical cascade that tells the muscle cell to relax

NO travels from inner lining of blood vessel to outer muscle layer very quickly

Explain how Sildenafil (Viagra) utilizes the nitric acid pathway

Sexual stimulation triggers endothelial cells to release nitric oxide. NO activates the intracellular receptor, which creates cyclic GMP. High levels of cGMP cause the smooth muscle wall of the blood vessel in the erectile tissue to gain a lot of blood. However, the enzyme PDE5 is used by the cell to make this response temporary. PDE5 immediately destroys cGMP.

Viagra works by directly binding to PDE5 and blocking its active site. It is a phosphodiesterase 5 inhibitor. Now, cGMP will not get broken down and keeps getting generated

As a result, the smooth muscles stay relaxed, and the blood vessels stay open so blood can flow through

What are the 4 steps of signaling cascades and what do they do?

Relay

Amplify

Integrate

Distribute

Describes what happens to the signal to get to the final cell response

Relay

Passes the signal from one intracellular protein to another. One effector protein activates the next protein in line

Amplify

Makes a weak signal into a stronger, louder signal by activating hundreds of effector proteins. The single enzyme activated by the receptor protein rapidly alters hundreds of thousands of proteins and all of those proteins alter thousands more.

Integrate

Takes signals from different signal molecules and combines them into one response. The cascade analyzes multiple messages before making a decision

Distribute

Sends the message to multiple effector proteins at the same time. The cascade splits up and sends instructions to different parts of the cell simultaneously

How do drugs and toxins have an effect on our body?

They can act on cell surface receptors since they are the same shape and size as a signaling molecule that already exists in our body. The cell receptor will respond to the drug because it is the same shape (lock and key model) and manipulates the already existing pathway

Acetylcholine is a

Neurotransmitter - carries messages from the brain to the rest of the body

How does nicotine have an effect on the body?

By mimicking the shape of acetylcholine. It binds to the receptor protein using the lock and key model and sends a bad signal (rush of dopamine and increased heart rate)

What does acetylcholine do

When you need to focus or learn, your brain releases acetylcholine, which is a signaling molecule that binds to the receptor proteins in order to pass the signal.

Drugs are

Exogenous chemicals - Made outside of the body

Signaling molecules are what type of chemical?

Endogenous chemical - naturally made inside of our body