11.1 Cell Signaling

Question 1

What are the methods of signaling covered in this lecture?

Answer 1

1) Contact- Dependent (Ex: Contact Dependent Gap Junction)

2) Paracrine (Ex: Autocrine)
3) Synaptic
4) Endocrine

Question 2

What is contact dependent signaling? Give an example

Answer 2

Signaling between two neighboring cells that touch (short distance).

Example: signaling through gap junctions. Small molecules and electrical depolarization evens can travel between two cells using gap junctions.

Ex: cells of the heart coordinate their contraction by signaling to each other through calcium signals that travel through gap junctions.

Question 3

What are the limitations of contact dependent-gap junction?

Answer 3

The molecules that travel via gap junctions must be small and can’t be complex. There is also no real control over the direction that a signal is traveling. Molecules simply diffuse across both cells.

Question 4

What is paracrine signaling? When is this type of signal used?

Answer 4

Used over moderate distances.

Signaling molecules are secreted by one cell and the secreted molecules are detected by other cells. The distances involved are short and there may be specific mechanisms involved to keep signals located to a small area.

Question 5

What is an example of paracrine signaling?

Answer 5

Surrounding cells that produce enzymes that degrade a signaling molecule, which will have the effect of limiting its effective range.

A lot of development events are regulated by paracrine signaling.

Question 6

What is a special example of paracrine signaling?

Answer 6

Autocrine signaling:

cells produce receptors that are activated by its own signaling molecules that it is also secreting. this type of system is used for both positive and negative feedback loops so that cells can control their own behavior through signaling.

ex: cancel cells signaling themselves to grow,

Question 7

What are two type of long distance signaling?

Answer 7

1) synaptic signaling

2) endocrine signaling

Question 8

Give examples discussed in lecture of endocrine signaling:

Answer 8

signaling by:

• Insulin
• Testosterone
• Estronen
• Growth hormones

Question 9

What is endocrine signaling?

Answer 9

Endocrine signaling uses the circulatory system to carry signals and there the signals are distributed throughout the body nonspecifically.

Question 10

What are some unique features of the endocrine system?

Answer 10

1) b/c signals are spread out through the entire body, their effective concentration is low since the individual contents are going to be diluted by the entire contents of the organism.
2) b/c of the above, receptors on the receiving end of the signal need to be able to detect small amounts of the signaling compound that are very highly diluted.
3) Molecules needs have high affinity with the receptor
4) Receptors have to be very specific and selective b/c target cells have to detect the appropriate molecule in the presence of signals that are intended for other cells
5) the distribution by blood flow takes time, so endocrine signaling is slow.

Question 11

What does high affinity mean? Which signaling system uses high affinity?

Answer 11

Endocrine system.

High affinity means when the molecule is present at low concentrations, the molecule being received by the receptors need to be bound very tightly

Question 12

Why is the endocrine signaling appropriate for events like digestion, growth, or development of gender specific features?

Answer 12

b/c the endocrine system is slow and these events are all slow as well.

Question 13

What is synaptic signaling?

Answer 13

Long distance signaling system. The initial signal is a nerve impulse that travels the distance of the neuron.This can be inches to feet in length.

At the nerve synapse, neurotransmitters are released which bind to a receptor on a target cell on the other side of the synapse.

The signaling molecule is not diluted b/c they don’t spread through the entire body. AKA they don’t have to bind so tightly to the receptors (high affinity is less than endocrine signaling)

Never impulses and diffusion occur quickly across the synaptic space. This type of signal is involved in events that require moderate speed such as changed in the diameter of blood vessels.

Question 14

How is synaptic signaling a selective process?

Answer 14

b/c a target cell may be attached to only one type of neuron.

Question 15

What is the difference between endocrine and synaptic signaling?

Answer 15

SYNAPTIC: signal molecules travel a short distance (inches to feet)
ENDOCRINE: signal molecules travel the entire body

SYNAPTIC: Receptors don’t need a very high affinity to signal molecule
ENDOCRINE:signal molecule and receptor need a very high affinity.

SYNAPTIC: signaling is involved in moderated speed events .
ENDOCRINE: signaling is involved in events that are slow.

Question 16

Give examples of fast response of target cells and slow response of target cells:

Answer 16

FAST: cell movement, secretion, enzyme activity. These events can occur within minutes of receiving a signal.

SLOW: changes in gene expression, cell growth, or changes in differentiation.

Question 17

How many types of receptor do target cells typically express?

Answer 17

They can express more than one, sometimes several, dozens, or hundreds.

This means cell have to constantly sort through a variety of signals to decide what they are supposed to be doing.

Question 18

Each target cell receives hundreds of signals and is programmed to respond in a distinct manner to each signal. What are four steps where this behavior is seen?

Answer 18

1) Survive - often takes more than one signal to tell a cell that it needs to survive.
2) Divide
3) Differentiate
4) Die - in the absence of the survival signal, the cell may die.

Question 19

In some cases, a single molecule binds to a receptor that is produced by two different types of cells and each cell responds differently even though the receptor is the same. What is an example of this?

Answer 19

Response of salivary glands and cardiac muscles to the neurotransmitter acetylcholine. They both respond to acetylcholine but the difference is caused b/c each cell has different internal signaling pathways. The trigger or receptor is the same but the response systems are different and takes different pathways.

Question 20

Specific cell response depends on what? Give examples discussed in lecture.

Answer 20

1) receptor presents on target cells and internal machinery by which cell integrates signal.
EXAMPLE: acetylcholine binds to same receptor but elicits distinct responses in heart muscle vs salivary gland cells

2) on the concentration of the signal that reaches the cell.

EXAMPLE:
This is commonly seen in embryogenesis, where the distance away from the sources of a signaling molecule determine the fate of the target cell. The signaling molecules involved are called morphogens b/c they alter morphogenesis or shape of the tissues/cells they are affecting.

Question 21

What are the two basic type of receptors?

Answer 21

1) Intracellular receptors

2) cell surface receptors

Question 22

What are intracellular receptors?

Answer 22

receptors that bind to ligands (molecules that bind receptor) that can enter a cell w/no assistance

Question 23

Molecules aka ligands that bind to intracellular receptors (w/no assistance) must be able to do what?

Answer 23

must be able to cross the cell membrane.

These ligands are typically small hydrophobic molecules like cholesterol and sterols. And b/c they are hydrophobic they are often transported to a target cell using a carrier system to prevent interaction w/the signaling molecule and the aqueous intracellular environment.

Question 24

How does the necessity of the ligand to cross the cell membrane severely constrain them?

Answer 24

It constrains the types of molecules that can be used for this type of signaling process. Most intracellular receptors are transcription factors that alter gene regulation in the nucleus of target cells.

Question 25

What are cell surface receptors? What are the three discussed in lecture?

Answer 25

cell surface receptors are transmembrane proteins with extracellular domains. Often the ligand doesn’t need to go inside the cel to function. as a result, cell surface receptors are much more adaptable and variable than intracellular receptors.

1) Ion channel receptor
2) G-protein coupled receptor
3) Enzyme couple receptor

Question 26

How do cell surface receptors alter gene expression?

Answer 26

they do so indirectly by activating intracellular proteins that enter the nucleus.

Question 27

What is the nuclear receptor family?

Answer 27

they are transcriptions factors that use intracellular receptors that bind to DNA

They share a
conserved DNA binding motif. The ligands bound by nuclear receptors are small
hydrophobic molecules, which look a lot like cholesterol molecules. These include the
sex hormones testosterone and estrogen, as well as vitamins like vitamin D, retinonic acid
which is derived from it

Question 28

What characteristics are displayed by ligands that bind to nuclear receptors?

Answer 28

small hydrophobic molecules which look a lot like cholesterol molecules. This includes, sex hormones testosterone and estrongen, vitamin D, retinonic acid and steroids

Question 29

What is the mechanism of activation of a nuclear receptor?

Answer 29

1) nuclear receptors are present in an inactive state in complex with an inhibitory protein.
2) the binding of the ligand displaces the inhibitory proteins and allows interaction w/ co-activator proteins.
3) This reveals the DNA binding domain which allows the receptor to bind to target gene promoters and recruit additional factors needed for gene transcription.

Question 30

What type of responses can activation of nuclear receptors have?

Answer 30

immediate early responses as well as longer term secondary responses.

Question 31

What are the three major subcategories of cell surface receptors?

Answer 31

1) ion channel-coupled receptors
2) G-protein coupled receptors
3) enzyme coupled receptors

Question 32

What are ion channel coupled receptors? What type of response do they cause?

Answer 32

Type of cell surface receptor.

These receptors open or close pores in the cell membrane in response to the ligand binding.

RESPONSE: the opening of such generates rapid changes in ion concentration w/in the cell such as calcium, sodium, or potassium.

Question 33

What are the G-protein coupled receptors?

Answer 33

Type of cell surface receptors.

These proteins work by activating another set of membrane associated proteins which is a complex with three proteins which use GTP as a secondary signaling mechanism.

Question 34

What are enzyme coupled receptors?

Answer 34

Type of cell surface receptor.

The receptor has an enzymatic function of its own that becomes functionally active when a ligand binds to them.

Question 35

What are the general steps of a signaling pathway?

Answer 35

1) Relay - Activity of protein is switched on. send the signal
2) transduce and amplify - binding of ligand to receptor must be converted into something that the inside of the cell can use (generation of second messenger) and it must be amplified.
3) integrate - cells must choose a specific pathway
4) spread
5) anchor - localize proteins to unique places in cells
6) modulate - signal needs to be converted into actions. Effector proteins are used to accomplish this task.

Question 36

What is scaffolding? What are the three examples discussed in lecture?

Answer 36

scaffolding helps convert ligand-to-receptor signal into intracellular response proteins. It does so by, physically tying early signaling events together. Scaffolding makes this process fast and efficient.

1) Scaffold protein: signaling complex is performed on scaffold protein
2) Activated Receptor scaffold: receptor itself has a large domain that will act as scaffold w/several binding domains
3) Phosphoinositide docking sites: assembly of signaling complex binds to this docking site

Question 37

What are the three different types of scaffolding?

Answer 37

1) Performed signaling complex on scaffold protein
2) assembly of signaling complex on an activated receptor
3) assembly of signaling complex on a phosphoionsitide docking sites

Question 38

Describe performed signaling complex on a scaffold protein

Answer 38

a very large scaffold protein w/multiple binding domains interact w/the activated receptor as well as several downstream signaling proteins that will convert the activation of the receptor into an intracellular signal.

Question 39

Describe assembly of signaling complex on an activated receptor (scaffolding)

Answer 39

the receptor itself has a very large domain that will act as a scaffold and has several binding domains.

Question 40

Describe assembly of signaling complex on a phosphoionsitide docking sites (scaffolding)

Answer 40

This involves the activation of phosphorylated lipids called phosphoionsitides in the adjacent membrane. These lipids can be localized to restricted regions or patch of a membrane. These can then form a localized area where downstream signaling molecules are first recruited then interact w/each other.

Question 41

Almost all signals will involve phosphorylation of some proteins on one of three amino acids. List the amino acids in order of frequency

Answer 41

1) Serine
2) Tyrosine
3) Threonine

Question 42

In signaling events, how are phosphate group added and removed (phosphorylation and dephosphorylated)? What does phosphorylation/dephosphorylation do?

Answer 42

ADDED: phosphate groups are added using a phosphate provided by ATP. This rxn is catalyzed by enzyme Kinase

REMOVED: phosphate groups are removed by enzymes called phosphatases.

ACTIVITY: the activity of a protein can be enhanced or decreased by phosphorylation. Phosphate groups are also removed to turn off signaling pathways.

Question 43

What are feedback systems?

Answer 43

feedback systems play important roles in shaping the response of cells to signals.

Question 44

What happens in the absence of feedback loops?

Answer 44

the signal generated by receptor activation would be a reflection of the number of ligands bound to receptors.

Question 45

What is a positive feedback system?

Answer 45

positive feedback system can generate the type of all or none response. Positive feedback can also prolong the response of a cell to a transient signal. Examples of this type of system include: developmental signals where a transient signal to differentiate creates a very long term change in the development fate of a cell.

a simply example of a possible mechanism of a positive feedback
system, in which a receptor catalyzes the production of activated molecules that then bind to and reactivate the receptor at another site.

Question 46

What trend is seen with all or none response when looking at the cell population as a whole?

Answer 46

it may show a graded response to the signal b/c not all cells are triggered at any one time. For example, secretion of insulin by the pancreas in response to a meal.It might be appropriate to have a graded response in which something other than the maximum amount of insulin is secreted into the blood stream. However, individual cells may be able to decide only whether or not to secrete the contents of their secretory granules as a whole.

Question 47

What are negative feedback systems?

Answer 47

this system has the effect of dampening or lowering the overall activity of a response system if there is little or no delay in the response of the various parts of the system.

Question 48

How are the different ways receptors are desensitized? what is the benefit of desensitizing a receptor?

Answer 48

1) Receptor sequestration: in an endosome, which can allow the receptor to be recycled to the cell surface or for degradation.
2) Receptor down-regulation: inactivates receptor (like neg. feedback loop)
3) Receptor inactivation
4) Inactivation of signaling protein
5) Production of inhibitory protein

EX: the sense of smell is rapidly desensitized in order to allow the system to respond to change in odors. This is beneficial b/c it allows an animal to detect new smells in the presence of another odor.