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BIO 317 > 12 - Second Messenger Signaling in Neuronal Development II > Flashcards

12 - Second Messenger Signaling in Neuronal Development II Flashcards

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1
Q

True or false: a protein localized all over the cell cannot act as a polarizing signal

A

False: the activation of this protein can be a polarizing signal

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2
Q

How can a protein that is localized all over the cell act as a polarizing signal?

A

In its specific activation by an activator in a specific location

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3
Q

Besides physical localization, how can a signal be localized?

A

Through its activation

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4
Q

How does LKB1 lead to axonal development?

A

Localized in the axon, and activated by PKA (from cAMP) in the axon

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5
Q

True or false: PAR-1 is localized within the neurite that will become the axon

A

False: PAR-1 is found everywhere in the neuron

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6
Q

How can PAR-1 lead to axon formation if it is not localized in the axon?

A

Its activation by LKB1 is localized within the axon

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7
Q

Which protein(s) are localized in a neurite to predict axon fate?

A

LKB1, phosphorylated LKB1, phosphorylated PAR-1

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8
Q

Which protein(s) are not localized in a neurite to predict axon fate?

A

PAR-1

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9
Q

What type of localization is seen with LKB1?

A

Physical and activation localization

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10
Q

What type of localization is seen with PAR-1?

A

Activation localization (not physical)

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11
Q

True or false: signaling pathways can interact with each other

A

True: they can converge or antagonize with each other to determine a biological function

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12
Q

True or false: neuronal development is an easy task

A

False: it is a fairly difficult and coordinated process

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13
Q

Why is neuronal development a hard task?

A

Hard to prolong a signal (as opposed to an on/off signal)

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14
Q

How long does axonal development take?

A

24-48 hours

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15
Q

What determines the output a signal will generate?

A
  1. The nature of the signal
  2. The strength / duration of the signal
  3. The signaling determinants a cell has
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16
Q

True or false: signals can be activating or inhibitory

A

True: the cell needs to integrate these signals to generate a response

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17
Q

Complete the sentence: signaling is ______, and it matters _____

A

Signaling is a well ordered set of instructions, and it matters how the instructions are arranged

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18
Q

What types of links are possible in signaling pathways?

A

Positive and negative

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19
Q

What is a positive link?

A

A activates B (A –> B)

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20
Q

What is a negative link?

A

A inhibits B (A –| B)

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21
Q

What is the schematic for a positive link?

A

A –> B

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22
Q

What is the schematic for a negative link?

A

A –| B

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23
Q

What does a double negative link result in?

A

A positive link

A –| B –| C = A –> C

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24
Q

What is fan in?

A

Multiple upstream regulators converge on one downstream target

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25
Q

What is fan out?

A

One upstream regulator diverges into many downstream targets

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26
Q

What is the consequence of a linear signaling arrangement?

A

One spark will end the signal (no feedback)

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27
Q

What is the consequence of a circular signaling arrangement?

A

Can continuously activate itself (positive feedback)

28
Q

What is a self regenerative pathway?

A

A pathway where a downstream effector can activate itself through a specific pathway

29
Q

What needs to be coupled to a positive feedback loop?

A

Negative feedback

30
Q

What is the significance of negative feedback in a positive feedback loop?

A

After some delay, can stop the signal and prevent it from continuing indefinitely

31
Q

Why is there a time consideration between the positive and negative feedback of a system?

A

Want the positive feedback to run for some time, but also to turn off eventually

32
Q

What is a feedback?

A

When the output from a given protein follows a path of links that return to regulate the proteins of origin

33
Q

True or false: there are different arrangements of positive and negative feedback

A

True: there are different ways the pathway can be set up

34
Q

True or false: you can get negative feedback through only positive links

A

False: there is no way to inhibit with only activation

35
Q

True or false: you can get positive feedback through only negative links

A

True: a double negative is equivalent to a positive

36
Q

How can kinases be used in positive feedback?

A

One kinase can phosphorylate other kinases, which can also activate the original kinase

37
Q

How can a ligand lead to positive feedback?

A

Promotion of more cell surface receptors (insertion or translation), or increased secretion of the ligand

38
Q

How can a ligand lead to negative feedback?

A

Internalization of the receptors

39
Q

How is positive feedback used in axonal development?

A

Persistent signal of polarization

40
Q

What is the PDZ domain?

A

A protein binding domain (PSD-95, Dlg-1, ZO-1)

41
Q

What do scaffold proteins do?

A

Bring signaling determinants to specific locations in the cell

42
Q

How can PKA be controlled?

A

By making it bind to a scaffold protein and localizing it within the cell

43
Q

How does the cell decide where to sequester PKA?

A

By where it wants PKA to be active

44
Q

How do scaffold proteins help PKA be active in a specific part of the cell?

A

By having all the upstream and downstream regulators of PKA also bound to the scaffold proteins

45
Q

What are the two specific roles of scaffolds?

A
  1. Sequester signaling determinants into specific locations of the cell
  2. Sequester signaling determinants needed for that particular protein to function
46
Q

What are the scaffold proteins studied in this positive feedback loop (polarization)?

A

PAR-3 and PAR-6

47
Q

What kinase binds to PAR-6?

A

aPKC

48
Q

What does aPKC bind to?

A

PAR-6

49
Q

What does aPKC stand for?

A

Atypical protein kinase C

50
Q

How are PKCs grouped?

A

By their mode of activation

51
Q

What is PKC?

A

A broad family of serine/threonine kinases

52
Q

What are the 3 major families of PKC?

A

Classical, novel, and atypical

53
Q

How is classical PKC activated?

A

Through calcium, DAG, and a phospholipid (PS)

54
Q

How is novel PKC activated?

A

Through DAG

55
Q

How is atypical PKC activated?

A

Through lipid second messengers (phosphatidylinositols) (not calcium or DAG)

56
Q

Which PKC is activated through calcium and DAG?

A

Classical

57
Q

Which PKC is activated through DAG?

A

Novel

58
Q

Which PKC is activated through phosphatidylinositol?

A

Atypical

59
Q

What is the structure of PKC?

A

A regulatory domain that inhibits the catalytic domain

60
Q

In cell polarization, what activated aPKC?

A

Binding of PAR-6 to the regulatory domain of aPKC

61
Q

What proteins bind to PAR-6?

A

PAR-3, aPKC, and Cdc42-GTP

62
Q

True or false: PAR-3 and PAR-6 associate together in the positive feedback loop

A

True: these two scaffold proteins join together many signaling determinants, and they are associated together

63
Q

How is PAR-6 an adaptor molecule?

A

It links Cdc42 and aPKC to PAR-3

64
Q

Where do PAR-3 and PAR-6 localize in epithelial cells?

A

At the apical domain

65
Q

What is the function of PAR-3 and PAR-6 in epithelial cells?

A

Determine the boundary of the apical and basolateral domain, recruit apical determinants, and exclude basolateral determinants

66
Q

Which PAR protein forms oligomers?

A

PAR-3

67
Q

What is the significance of PAR-3 forming oligomers?

A

It leads to robust recruitment of scaffold proteins (and therefore signaling determinants)

BIO 317 (27 decks)

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