Secondary Messengers

Question 1

Secondary messengers mediate ___ signalling

Answer 1

intracellular

Question 2

List 3 types of indirect transmission of signals

Answer 2

1) endocrine signalling
2) paracrine signalling
3) synaptic signalling

Question 3

List 3 types of signalling molecules

Answer 3

1) cell impermeant molecules - require a receptor
2) cell permeant molecules - molecule diffuses right across membrane
3) cell surface signalling molecules - signaling occurs through direct binding of 2 cells close together

Question 4

Is GPCR signalling slow or fast? Why?

Answer 4

Slow due to the time it takes to generate a signal cascade

Question 5

Is ionotropic signalling considered fast or slow? Why?

Answer 5

Fast bc the ion channel opens, immediately allowing ions to flow through which allows the cell to quickly summate it and turn the signal into “make AP” or “don;t make AP”

Question 6

Where in the synapse are metabotropic receptors located?

Answer 6

perisynaptic/peripheral area

Question 7

T or F: activating only a few metabotropic receptors will yield a large effect

Answer 7

T

Question 8

T or F: activating only a few ionotropic receptors will yield a small effect

Answer 8

T

Question 9

Where is the NT binding site located on metabotropic receptors?

Answer 9

Middle of the channel

Question 10

Do metabotropic receptors have large extracellular domains?

Answer 10

No

Question 11

What do GAP proteins do?

Answer 11

Controls speed of GTP hydrolysis (GTP is bound to monomeric G protein)

Question 12

Which enzyme is responsible for replacing GDP on monomeric G protein with GTP?

Answer 12

GEF

Question 13

Name a common monomeric G protein

Answer 13

Ras

Question 14

In a heterotrimeric G protein, which subunit acts as the GTPase?

Answer 14

alpha

Question 15

Which subunit in a heterotrimeric G protein binds GTP?

Answer 15

alpha

Question 16

What acts the GEF in a heterotrimeric G protein?

Answer 16

GPCR - activated GPCR allows alpha-GDP to be replaced with GTP

Question 17

T or F: Only the alpha subunit of a G protein can activate downstream effectors

Answer 17

F - the beta/gamma subunit can as well

Question 18

Which subunit of a heterotrimeric G protein is membrane bound?

Answer 18

Gamma

Question 19

In basal state (ie not bound to a NT), is the GPCR associated with a G protein?

Answer 19

No

Question 20

What does the Gi subunit do?

Answer 20

Inactivates adenylyl cyclase, leading to decreased cAMP production

Question 21

What does Gq do?

Answer 21

Activates PLC, which generates IP3 + DAG

Question 22

What kind of enzymes cleave IP3 to stop it from signalling? What is it cleaved into?

Answer 22

Phosphatases; inositol

Question 23

Which molecule is DAG and IP3 generated from?

Answer 23

PIP2

Question 24

Is DAG transmembrane or soluble?

Answer 24

transmembrane

Question 25

What does DAG activate?

Answer 25

PKC

Question 26

Which cycle do IP3 and DAG undergo to regenerate PIP2?

Answer 26

Phosphoinositol cycle

Question 27

Which ion can be used to block the phosphoinositol cycle?

Answer 27

lithium

Question 28

Which alpha subunit can be used to turn on ECB production?

Answer 28

Gq

Question 29

In PKA, what does the regulatory domain act as?

Answer 29

pseudosubtrate to prevent catalytic kinase domain from being active all the time

Question 30

Describe how GPCR signalling affects PKA activity

Answer 30

1. alpha subunit (Gs) activates AC 2. AC generates more cAMP 3. cAMP binds to regulatory domain on PKA, causing conformational change that releases the catalytic domain

Question 31

Which calcium binding protein activates CaMKII?

Answer 31

calmodulin

Question 32

PKC is activated by ___ and coactivated by ___

Answer 32

DAG, Calcium

Question 33

Name 4 categories of cellular receptors

Answer 33

1. channel linked receptors/ionotropic 2. enzyme linked receptors (ex. RTKs) 3. intracellular receptors 4. GPCRs/metabotropic

Question 34

T or F: Ca is an intracellular secondary messenger

Answer 34

T

Question 35

Name 2 sources of Ca:

Answer 35

1. extracellular space | 2. ER

Question 36

T or F: Normally, intracellular concentrations of Ca are quite how

Answer 36

F - they are normally LOW

Question 37

List 5 intracellular targets of Ca

Answer 37

``` Synaptotagmin kinases phosphatases calmodulin ion channels ```

Question 38

List 3 Ca removal mechanisms

Answer 38

1) Ca exchangers and Ca pumps on plasma membrane 2) Ca pumps on ER membrane 3) mitochondria acts as a temporary Ca sink

Question 39

List a ligand-gated channel that will allow Ca to enter the cell

Answer 39

NMDA, an ionotropic glutamate receptor

Question 40

What activates the ryanodine channel on ER?

Answer 40

Calcium - generates a positive feedback loop for Ca release

Question 41

How will an axon terminal with many mitochondria affect the length of time that the NT signals for?

Answer 41

The mt will sequester the Ca which is needed for NT release, therefore the synapse will not be able to signal for very long

Question 42

How will an axon terminal with few mt affect signalling?

Answer 42

Ca will rise quickly because there are less mt to sequester it, therefore more signalling will occur since more vesicle fusion will occur

Question 43

If you want more release of dense core vesicles, would your axon terminal require more or less mitcohondria?

Answer 43

Less - allows Ca levels to rise more quickly

Question 44

What is the main purpose of CaMKII autophosphorylation?

Answer 44

Maintenance of Ca signal even after Ca is gone

Question 45

T or F: many interneurons contain buffering CBP

Answer 45

T

Question 46

Do buffering CBP cause downstream signalling?

Answer 46

No

Question 47

Which proteins may be used to label interneurons?

Answer 47

Buffering CBP

Question 48

How to Ca-binding dyes work?

Answer 48

They change their fluorescence when they bind to Ca

Question 49

High Ca levels will result in increased phosphorylation or dephosphorylation?

Answer 49

High Ca --> activate kinases --> high phosphorylation

Question 50

Low Ca levels will result in increased phosphorylation or dephosphorylation?

Answer 50

Low Ca --> activate phosphatases --> high dephosphorylation