Cell Communication

Front 1

What receives the signal in most cases of cell communication?

Back 1

a receptor protein on the target cell

Front 2

What are the 4 mechanisms of cell communication?

Back 2

1. Contact Dependent Signaling
2. Paracrine Signaling
3. Synaptic Signaling
4. Endocrine signaling

Front 3

What is contact dependent signaling?

Back 3

-relatively rare
-no chemical released
- cells have to come into very close contact
- Important during embryonic development

Front 4

What is paracrine signaling?

Back 4

-common
- can target multiple, neighbouring cells
- doesn't go very far (local)
-signal is released by exocytosis and acts on multiple neighbouring targets (paracrine)
- or on the signaling cell itself (autocrine)
- acts as a feedback mechanism that allows the cell to control the signal

Front 5

What is the difference between Paracrine and autocrine?

Back 5

Paracrine- in paracrine signaling, when the signal acts on multiple neighbouring targets

Autocrine: when the signal acts on the cell itself.
- feedback mechanism that allows the cell to control the signal

Front 6

What is synaptic signaling? Where does it function?

Back 6

- Only functions on cells of the nervous system
- equivalent to "face to face conversation"
- signal is produced by a neuron and released at a synapse; acts on a single postsynaptic target

Front 7

What is endocrine signaling?

Back 7

- When a hormone is released by exocytosis, it is released into the blood stream and can reach cells that are far away
- acts on multiple cells

Front 8

What kind of cell produces hormones?

Back 8

an Endocrine cell

Front 9

What types of signaling target multiple cells? What kind target single cells?

Back 9

Multiple cells
- Paracrine Signaling
-Endocrine Signaling

Single cell
- Synaptic signaling
-Contact dependent signaling (I'm only 90% sure about this)

Front 10

- What are the types of signaling molecules? Which is most common? Least common?

Back 10

-hydrophilic (most common)
-hydrophobic
-gases(least common)

Front 11

List examples of hydrophobic signaling molecules. What are they generally?

Back 11

generally, they are proteins, peptides, derivative amino acids, and small organic molecules

Acetylcholine
- a neurotransmitter

Adrenaline
- small, organic molecule that functions as a hormone

Growth factors
- most often used in paracrine signaling

Front 12

In what kind of signaling are growth factor proteins commonly used?

Back 12

Paracrine signaling

Front 13

Signaling molecules are _________ in animal phyla

Back 13

conserved

Front 14

Give an example of a hydrophobic signaling molecule

Back 14

Steroid hormone

Front 15

Give an example of a gas signaling molecule

Back 15

Nitric oxide

Front 16

How does a hydrophobic signal or gas signal bind to a receptor?

Back 16

-since it is hydrophobic, it can permeate the target cell and bind to either cytosolic receptors or nuclear receptors

-goes right through the cell membrane

Front 17

what kind of signal type are protein kinases (usually)?

Back 17

Hydrophobic

Front 18

How does a hydrophilic signal bind to a receptor?

Back 18

-hydrophilic signals cannot permeate the membrane.

- bind to cell surface receptor, making them an extracellular receptor

1. binds to surface receptor
2. alters the intracellular protein, which acts like an intermediate protein (cascade effect)
3. Target protein is then affected

Front 19

How is the target protein effected in extracellular signaling? What type of signal does extracellular signaling

Back 19

1. binds to surface receptor
2. alters the intracellular protein, which acts like an intermediate protein (cascade effect)
3. Target protein is then affected

- signal type: hydrophilic

Front 20

If the target protein of extracellular signaling is a metabolic enzyme, what happens?

If it's a gene regulatory protein?

if it's a cytoskeleton protein?

Back 20

Metabolic enzyme- would alter metabolism

Gene regulatory protein- altered gene expression

cytoskeletal protein- altered cell shape or movement

Front 21

What determines the response that an extra cellular signal will cause (i.e. Acetylcholine)?

Back 21

Determined by type of cell-surface receptor on diff. cells
ex.
A) in a heart muscle cell
- Acetylcholine binds, causes muscle to elongate then relax.
-decreased rate and force of contraction
B) Salivary gland cell
- Acetylcholine binds, causes secretion
C) Skeletal muscle cell
- Acetylcholine binds to receptor on muscle
- contraction

Front 22

What are the properties of fast and slow responses in cell signaling?

In other words, what makes a fast response fast, and a slow response slow?

Back 22

Fast response: involves changes in existing proteins

Slow response: requires new protein synthesis

Front 23

Steroid Hormone:

- What is it derived from?
-how does it reach the target cell?
-what are its important functions?

Back 23

-Derived from cholesterol
- dispersed through blood, (endocrine signaling)
-Functions: controls metabolism, immune function, development of male/female sexual characeristics

Front 24

What is the process of a steroid hormone causing translation of a gene? (general, from receptor binding to translation)

Back 24

-Steroid binds to receptors in the cytosol, then moves to nucleus
OR - steroid binds straight to nucleus receptors

- in nucleus, steroid receptor complex binds to DNA, which turns on gene expression (that is a slow response)
- binding causes genes to be transcribed
-leads to translation

Front 25

What type of protein are steroid Receptors?

Back 25

DNA=binding proteins

Front 26

What part of steroid receptors is highly conserved?

In other words, what is the same in all Steroid receptors?

Back 26

DNA binding domain

Front 27

What is the DNA binding domain of steroid receptors consist of?

Back 27

Two zing fingers that bidn to specific DNA sequences called Hormone Response Elements

Front 28

What are Hormone Response elements?

Back 28

DNA sequences to which the DNA binding domains of Steroid Receptors bind.`

Front 29

What makes a steroid receptor inactive?

Back 29

The nuclear localization signal is bound by an inhibitory protein ( a chaperone)

Front 30

What are the parts of an empty steroid receptor?

Back 30

Ligand binding domain
transcription activating domain
DNA binding domain

Front 31

What does the steroid receptor look like as soon is it is activated?

Back 31

-A ligand is attached
- Coactivator proteins are attached to the ligand-binding domain and transcription activating domain
- Only the DNA binding domain is exposed

Front 32

Once the hormone is in the steroid receptor, how do Steroid hormones activate gene expression? (specific)

Back 32

1. Receptor-steroid-hormone complex activates primary response genes.
2.Primary (early response) genes are transcribed
3. Proteins encoded by these genes (primary response proteins) turn on expression of secondary delayed response genes
4. Secondary response proteins synthesized

Front 33

What are the three types of cell-surface receptors?

Back 33

1. Ion-channel linked receptors
2. G protein-coupled receptors
3. Enzyme-linked receptors

Front 34

what are the structural characteristics of GPCRs?

Back 34

7 transmembrane domains

N- terminal in extracellular matrix, C- terminal in side the cell

3 loop of intracellular loop is bigger than the others

Front 35

What part of GPCR is important for binding the extracellular signals? the intracellular signals?

Back 35

extra-cellular: N-terminal

Intra-celular: Cterminal and 3rd intracellular loop

Front 36

What intermediate is needed for GPCR to activate a target?

Back 36

a G-protein

Front 37

What is an orphan receptor?

Back 37

a receptor for which the gene exists, and it is expressed, but we don't know what activates it

many are probably activated by smell/taste

Front 38

What is the structure of a G-protein? What are its general physical properties?

Back 38

-Trimeric, has three subunits (alpha,beta, gamma)
-has GTPase activity
-lipid-anchored membrane protein

Front 39

what does the alpha subunit do in G-proteins?

Back 39

it binds and hydrolyzes GTP and GDP

Front 40

What are the three major classes of G proteins?

Back 40

Gs
Gi
Gq

Front 41

What does the inactive form of G protein look like compared to the active form?

Back 41

Inactive is trimeric, and has GDP

Active has dissociated subunits, GTP

Front 42

How do the three subunits of the G protein dissociate?

Back 42

Alpha splits from (beta and gamma), all three remain attached to the membrane

Front 43

What is the first thing that happens when a signal binds to GPCR?

Then what?

Back 43

A conformational change in the receptor occurs, causing GPCR to have a higher affinity for G protein/binds more tightly to g protein

Then, G protein undergoes a conformational change, causing it to replace GDP with GTP

After this, protein is fully activated?

Front 44

Which subunit(s) of g protein act like an on/off switch? How?

Back 44

G alpha subunit, because it binds to a target protein which creates altered protein activity (on)

after a while, G alpha subunit hydrolyzes GTP and dissociates from the target (off)

Front 45

What happens to G alpha subunit once it dissociates from its target protein?

Back 45

It re-associates with G beta/G gamma subunits, making the G protein inactive once more.

Front 46

What is the most common target of G proteins?

Back 46

Adenylate Cyclase enzyme

Front 47

What activates adenylate cyclase? what inhibits it?

Back 47

Gs alpha activates

Gi alpha inhibits

Front 48

what activates phospholipase c-beta?

Back 48

Gq alpha

Front 49

What produces cyclic AMP (cAMP)?

Back 49

adenylate cyclase

Front 50

When would you see cAMP in a cell? when would you not see it? Why would you start/stop seeing it?

Back 50

you would see it when the enzyme Adenylate cyclase is activated.

you would stop seeing it once the signal for Adenylate cyclase activation has ceased (once GCPR is not binding to a signal)
- because cAMP is quickly destroyed by phosphodiestherase

Front 51

What does cAMP activate?

Back 51

Protein Kinase A (PKA)

Front 52

What is the structure of Protein Kinase A (PKA)?

Back 52

4 subunits, 2 catalytic, 2 regulatory

Front 53

What role do the subunits of PKA play?

Back 53

they bind to cAMP (4 cAMP are needed to activate a protein kinase)

once cAMP is bound, it causes the dissociation of PKA complex, which releases the catalytic subunits that can phosphorylate other proteins

Front 54

how many cAMP are needed to activate a PKA?

Back 54

4

Front 55

What's an example of a serine-thrionine protein kinase?

Back 55

PKA

Front 56

What enzyme has broad specificity and catalyzes reactions at serine/thrionine residues?

Back 56

PKA

Front 57

is cAMP fast or slow? why?

Back 57

fast, doesn't need to do protein synthesis

Front 58

Give an example of an intracelllular second messenger. What makes it an intracellular second messenger?

Back 58

cAMP, because the 1st messenger would be the extracellular signal that causes the formation of cAMP
- then cAMP is the second, because it then activates PKA

-cAMP necessary because the hydrophilic 1st signal cannot get in the cell

Front 59

When would cAMP be considered fast response?

slow response? what happens here?

Back 59

cAMP is fast during its regular activity in activating PKA, because no proteins need to be synthesized.

cAMP is slow when it stimulates gene expression
- less common
- happens when PKA can get into the nucleus via nuclear pores
- causes the nuclear protein CREB to be phosphorylated
-CREB is a gene regulatory protein, which causes new proteins to be syntehsized when it is phosphorylated

Front 60

What is a CREB?

Back 60

a nuclear, gene-regulatory, protein that is phosphorylated by PKA via slow response (when PKA goes straight into nucleus, stimulated by cAMP)

Front 61

What are the 4 ways a cell can stop the response to a signal in G-protein coupled receptor signaling?

Back 61

1) no more signal is made, means no more G-protein is made, which causes a cascade
2) If the G-alpha subunit turns itself/g-protein off by hydrolyzing GTP
3)if the enzyme that destroys cAMP (phospho-diestherase) becomes active
4) if the protein phosphatases that remove phosphates become active

Front 62

how does signal desensitization occur? Why does it occur?

Back 62

Occurs in response to a signal that continuously keeps being delivered (for example by a stress related hormone)
- receptor is constantly full of signal, keeps being activated, needs to be "quieted"
- after some time, receptor becomes desensitized by repeated ligand stimulation
-if the signal is present in the receptor for too long, the receptor will be phosphorylated, causing a conformational change

Front 63

What does Adrenaline stimulate in the muscle and liver?

Back 63

- glycogen phophorylate

Front 64

What mediates the effect of Adrenaline stimulus? Why?

Back 64

a GPCR called beta-adrenergic receptor
- Because the hormone is outside of the cell, it needs a GPCR to send the signal inside

Front 65

what is the path of the Adrenaline signal in turning on Glycogen Phosphorylase?

Back 65

1. Adrenaline binds to beta-adrenergic GPCR (associated with Gs
2.G protein activated
3.Adenylate cyclase activated
4.causes production of cyclic AMP
5. Makes PKA active
-PKA, although it has broad specificity, does not recognize Glycogen phosphorylase, so there needs to be an intermediate
6.PKA activates phosphorylase kinase (PK)
- via phosphorylation
-PK specifically phosphorylates Glygogen phosphorylase
7. PK phosphorylates GP, activates it
8. Glycogen brokedown into Glu-1-P

Front 66

What breaks down cAMP immediately after it is produced (pretty much immediately after)?

Back 66

cAMP phosphodiestherase

Front 67

How does signal amplification occur?

Back 67

it is the by-product of signal cascade
- everytime a reaction step occurs, you intensify teh signal because more and more molecules are involved
ex. PKA activated
- 1 molecule PKA, phosphoryaltes many PK
- each PK phosphporylates many GP

Front 68

what are several examples of intracellular second messengers?

Back 68

cAMP

Calcium

inositol triphosphate, GMP

Front 69

explain how Calcium acts as a an intracellular second messenger.

Back 69

Calcium increases rapidly in stimulated cells, proteins activated
ex. Calcium/calmodulin-dependent protein kinases (CaM kinases)
ex. Protein Kinase C (PKC)
ex. Calcineurin (Phosphatase)
ex. Troponin (actin-binding proteins)

Gq and phospholipase C-beta signaling pathway
- uses inositol phospholipid.Calcium pathway
- used in control of regulated secretion/exocytosis
-phospholipases c-beta cleaves phosphoinositol biphosphate (PIP2)
- reaction produces inositol triphosphate (IP3) and Diacylglycerol

Front 70

What is IP3 (Inositol triphosphate)? What does it do?

Back 70

a product of the Phospholipase C-Beta signaling pathway
- IP3 travels to ER and opens channel of ER membrane
- ligand gated channel
-Calcium released into cytosol

Front 71

what are all thre major pathways in eukaryotic intracellular communication?

Back 71