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BIO 317 > 15 - Signaling Mechanisms Underlying Axon Guidance I > Flashcards

15 - Signaling Mechanisms Underlying Axon Guidance I Flashcards

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1
Q

What question can be asked regarding redundancy?

A

Do we have redundancy, or are some proteins critical for functioning

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2
Q

True or false: there are neuropathologies associated with LKB1

A

False: there are no neuropathies associated with LKB1

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3
Q

What is STRAD?

A

A cofactor for LKB1

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4
Q

What is the cofactor of LKB1?

A

STRAD

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5
Q

In basal conditions, where is LKB1 located?

A

In the nucleus

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6
Q

In basal conditions, where is STRAD located?

A

In the cytoplasm and in the nucleus

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7
Q

What do STRAD and MO25 do to LKB1?

A
  1. Phosphorylate it at Ser431 to activate it

2. Localize LKB1 into the cytoplasm to function

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8
Q

What would happen to a cell without STRAD?

A

LKB1 would be localized in the nucleus

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9
Q

What functions does LKB1 have in the nucleus?

A

Unknown, but it cannot mediate its downstream targets for cell polarization

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10
Q

True or false: there are neuropathologies associated with STRAD

A

True: PMSE is associated with a truncated STRAD gene

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11
Q

What are the symptoms of PMSE?

A

Psychomotor disability, epilepsy, and early childhood mortality

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12
Q

Why does PMSE lead to neuronal problems?

A

The truncated STRAD cannot localize LKB1 into the nucleus for proper axon formation

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13
Q

How come there are no pathologies associated with LKB1?

A

It is a critical enzyme, and thus its deletion is lethal (embryonic death)

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14
Q

How come there are pathologies associated with STRAD?

A

It is important, but not critical, for axon development, so people can still survive (other mechanisms)

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15
Q

What happens to STRAD in PMSE?

A

It gets truncated

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16
Q

What is the importance of crosstalk?

A

Regulation, specificity, redundancy, and amplification

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17
Q

What are the components of a signaling pathway (for an intricate and regulated pathway)?

A

On/off processes with time delays

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18
Q

What is a feed forward mechanism?

A

A signaling mechanism originates at one upstream regulator, and converges on one function

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19
Q

True or false: for a feed forward mechanism, the paths must be the same

A

False: the paths (signaling determinants) can be different, but the start and end points have to be the same

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20
Q

True or false: for a feed forward mechanism, the start and end points must be the same

A

True: the paths (signaling determinants) can be different, but the start and end points have to be the same

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21
Q

What is the advantage of a feed forward mechanism?

A

It is a relentless signaling to activate a critical function

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22
Q

True or false: the paths in a feed forward mechanism must converge at the same time

A

False: there can be time delays between the different paths, as long as they converge on the same function

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23
Q

What is the difference between a feedback and a feed forward?

A

A feedback loops back onto an upstream regulator, while a feed forward moves forward towards a downstream function

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24
Q

What is coupled to a positive feed forward mechanism?

A

Negative regulation (with a time delay)

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25
Q

What is coherent feed forward?

A

When the two branches have the overall same sign

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26
Q

What is incoherent feed forward?

A

When the two branches have the opposite signs overall

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27
Q

True or false: a coherent feed forward can be positive or negative

A

True: as long as the overall messages of each branch are the same, it is a coherent feed forward

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28
Q

True or false: a positive coherent feed forward can only have positive linkages

A

False: only the overall message of the branch needs to be positive (A –| B –| C = A –> C)

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29
Q

True or false: a negative coherent feed forward can only have negative linkages

A

False: only the overall message of the branch needs to be negative (A –> B –| C = A –| C)

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30
Q

True or false: a coherent feed forward must have the same linkages

A

False: they only need to communicate the same overall message (A –| B –| C = A –> C)

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31
Q

True or false: an incoherent feed forward must have different linkages

A

False: they only need to communicate different overall messages (A –| B –| C = A –> C)

32
Q

What is the relationship between the cAMP pathway and the PI3K pathway in polarization?

A

A coherent feed forward

33
Q

What does GSK3b stand for?

A

Glycogen synthase kinase 3 beta

34
Q

What does GSK3b do?

A

Regulates glycogen synthesis, and mediates polarization (and other functions)

35
Q

When GSK3b is phosphorylated, what state is it in?

A

Inactive

36
Q

When GSK3b is not phosphorylated, what state is it in?

A

Active

37
Q

What is the natural state of GSK3b in the cell?

A

Constitutively active

38
Q

What enzyme inactivates GSK3b?

A

Akt

39
Q

What enzyme sits in the middle of the crosstalk between the cAMP and PI3K pathway?

A

GSK3b

40
Q

Which amino acid regulates GSK3b function?

A

Ser9

41
Q

What state does GSK3b need to be in to promote axon development?

A

Inactive (phosphorylated) state

42
Q

What is a downstream effector of GSK3b?

A

CRMP-2

43
Q

What is the upstream regulator of CRMP-2?

A

GSK3b

44
Q

What does CRMP-2 do?

A

Regulates microtubule formation

45
Q

When CRMP-2 is phosphorylated, what state is it in?

A

Inactive

46
Q

When CRMP-2 is not phosphorylated, what state is it in?

A

Active

47
Q

What state does CRMP-2 need to be in to promote axon development

A

Active (non phosphorylated) state

48
Q

What does CRMP-2 stand for?

A

Collapsin-response mediator protein 2

49
Q

What is one of the most downstream effectors of axon formation and development?

A

Microtubule regulation

50
Q

What is the growth cone?

A

The tip of the neurites

51
Q

What is the tip of the neurite called?

A

The growth cone

52
Q

What happens at the growth cone?

A

Signaling for axonal development occurs, with constant shape changes

53
Q

True or false: the growth cone is a static structure

A

False: it is highly dynamic

54
Q

Where are the signaling pathways for axonal development centralized?

A

In the growth cones

55
Q

What is the structure of the growth cone?

A

Rich in actin and microtubule cytoskeleton

56
Q

What is the majority of the growth cone comprised of?

A

Actin cytoskeleton

57
Q

What does the actin cytoskeleton do in the growth cone?

A

Monitors and responds to the environment

58
Q

What does the microtubule do in the neurites?

A

Builds the stem of the neurites

59
Q

True or false: the actin and microtubule cytoskeletons in the growth cone do not interact

A

False: the microtubule can invade the actin network and regulate the shape of the growth cone

60
Q

What does the growth cone respond to?

A

Gradients of extracellular cues

61
Q

How does the growth cone respond to extracellular cues?

A

Through its receptors

62
Q

Where are the receptors to respond to extracellular cues (for axon formation) found?

A

In the growth cone

63
Q

What is the structure of the microtubules?

A

A hollow cylinder

64
Q

What are the monomers of the microtubules?

A

GTP-bound alpha and beta tubulin

65
Q

How many filaments comprise a microtubule?

A

13 filaments

66
Q

True or false: the microtubules are static structures

A

False: they are highly dynamic (can grow and shrink)

67
Q

True or false: microtubules are symmetrical

A

False: they have directionality (plus and minus end)

68
Q

What happens at the plus end of microtubules?

A

Adds tubulin subunits

69
Q

What happens at the minus end of microtubules?

A

It gets degraded

70
Q

What do plus end stabilizer proteins do?

A

Bind to the plus end of the microtubule and stabilize it (no synthesis)

71
Q

How does CRMP-2 work?

A

It binds to tubulin monomers and incorporates them into the microtubule

72
Q

Why does CRMP-2 need to be not phosphorylated to mediate microtubule formation?

A

It has a lower affinity for tubulin when it is phosphorylated

73
Q

When is CRMP-2 inactived?

A

When GSK3b is activated

74
Q

When is CRMP-2 activated?

A

When GSK3b is inactivated

75
Q

What happens to the cell when GSK3b is inhibited?

A

Multiple axons form

76
Q

What happens to the cell when GSK3b is constitutively activated?

A

No axons form

77
Q

What is needed in the axon (in terms of GSK3b and CRMP-2) to promote axonal development?

A

Unphosphorylated (activated) CRMP-2 and phosphorylated (inactivated) GSK3b

BIO 317 (27 decks)

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