Cell Communications

Primitive Cell Signaling - beginning of cell signaling

• Yeasts communicate between 2 types of yeast cells to reproduce. 

• 2 sexes, a and alpha - secrete specific signaling molecule, a factor and alpha factor.

• Factors find each other and bind to each other’s receptors

• Bacteria can release chemicals when resources are scarce that trigger neighboring bacteria (of the same species) to clump together and form spores (resistant to environmental conditions)

• Bacteria are able to regulate their own concentration to allow them to work together. 

For example, biofilms are created when bacteria stick to a surface where they can get their nutrition, just like the ones created on your teeth when you don’t brush properly.

Long Distance and Local communications

Local signaling:

• Direct contact (cell junctions) - cytoplasm of neighboring cells are connected.

• Cell-to-cell recognition - important in embryonic development (which way is up? Where will the liver go?) and immune response (you don’t belong here so I am going to attack you)

• Short distances: paracrine signaling

Example: growth factors that stimulate nearby and target cells to….grow

• Synaptic signaling - nerve cell produces neurotransmitter that diffuses to single cell - is almost touching sender. 

• Nerve signals travel along series of nerve cells without unwanted responses from other cells.

Ion - channel receptors

• Ligand-gated ion channel - this channel can open and close in response to the ligand binding (or not)

  • When open, it allows certain ions to be able to flow through the channel.

  • When closed - not happening.

• This is SUPER important in the nervous system!

Longer distance signaling

• Hormones!

• Cells release hormones that travel to other parts of the body until they reach target cells that respond to the chemicals.

• How does that work? 

The signal transduction pathway.

Signal Transduction Pathway - Step 1: Reception

• The target cell receives the signal.

• This happens when the molecule that is being used to signal binds to the receptor at the surface of the cell.

  • Signal molecule is complementary to the receptor protein.

• The signaling molecule acts as a ligand; a molecule that binds to another molecule.

  • This causes the receptor to change its shape which can activate the receptor (so that it can interact with other molecules)

  • Many diseases are associated with malfunctions in receptors (asthma, cancer, heart disease).

    • Some breast cancer patients have an excessive amount of receptors - proteins have been created that can bind to those receptors, thus blocking signals telling the cells to grow and divide.

Transmembrane receptor types:

G protein-coupled receptors:

• These are the largest group of receptors in the body.

• Epinephrine, neurotransmitters and many other hormones use these receptors.

  • When the protein is activated (by a signal molecule), GTP replaces GDP (activates the G protein)

• The G protein leaves the receptor, and then binds to an enzyme that can trigger the next step (leading to a cellular response)

  • The G protein will leave the enzyme which resets the process (the enzyme is inactive)

  • More ligand outside the cell leads to more activation of the enzyme.

  • In this way, it acts as on/off switch; cycles between being active and inactive.

• Receptor tyrosine kinase (RTKs):

• These are enzymes that start the process of transferring phosphate from ATP to another protein (specifically tyrosines)

• Once the ligand has bound to the RTK, it can activate 10+ different transduction pathways at once!

  • RTKs that are abnormal (as in they function without the need for the signaling molecule) are the cause of many types of cancers.

• Step 2: Transduction

• The binding of the molecule changes the protein receptor (this can happen in lots of different ways)

• This stage converts the signal to some form that brings a response inside the cell (this is the signal transduction pathway)

Signal Transduction Pathways

• Signal transduction pathway - the chain of interactions that leads to a cellular response.

• Relay molecules are often proteins (cell-to-cell signaling often involves proteins)

To activate a protein, you need to add a phosphate group to it (phosphorylation), which is done by a protein kinase (enzyme)

• Can be done through phosphorylation cascade - when a series of different proteins are phosphorylated (“turned on”). 

  • This can activate other proteins (a “cascade”)

• Signals can be turned “off” through enzymes that can remove phosphate groups (dephosphorylation)

• Some pathways include signals that are water-soluble (second messengers).

  • Because they are water soluble, they can easily spread throughout the cell via diffusion.

  • Cyclic AMP is one of those signals that is a molecule produced by ATP that elicits cellular responses.

  • Some responses can be initiated by increases in Ca+ ions

• Some pathways include signals that are water-soluble (second messengers).

  • Because they are water soluble, they can easily spread throughout the cell via diffusion.

  • Cyclic AMP is one of those signals that is a molecule produced by ATP that elicits cellular responses.

  • Some responses can be initiated by increases in Ca+ ions

What’s the End Product:

• The goal is to regulate cell activities which can occur in the nucleus or in the cytoplasm.

• This can turn genes on or off which would ultimately regulate protein synthesis.

• The signal can be amplified (made a lot bigger) where the products in one step are bigger than the previous step.

  • This allows for a bigger response to a signal without having to utilize too many signal proteins.

Increasing the efficiency of the signal

• Though it appears as if the relay molecules are all over the cell, this would not be a proper set-up.

  • WHY???

  • The relay molecules are usually proteins and cannot diffuse quickly through the thickened cytosol.

• Reality?

• Proteins that are able to relay the message to several other proteins at once are used (scaffolding proteins)

• These are found in places like the brain, where synapses need to be able to move quickly.

• Binding of the signal proteins is reversible…

  • Because the signal cannot last forever!

• As the concentration of signaling molecules falls, there are fewer receptors being used. 

  • Responses can only occur when the concentration of receptors in use is a certain amount (threshold)

  • If cells are damaged, they can undergo programmed cell death (apoptosis)

    • This is done by destroying the DNA and all the cell parts.

    • The cell shrinks and the parts are packaged up in vesicles that are destroyed by scavenger cells.

    • This prevents nearby cells from being damaged from leakage from the damaged cell.