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BB20028 > Axonal guidance and synapse formation > Flashcards

Axonal guidance and synapse formation Flashcards

1
Q

What does synapse formation allow?

A

Neuronal survival.

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2
Q

What are junctions between nerve cells and muscle cells called?

A

Neuromuscular junctions.

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3
Q

What happens to neurons that do not connect with targets?

A

They undergo apoptosis.

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4
Q

Around how many neurons die that are formed in the spinal cord?

A

Around half of the 20,000 that are formed.

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5
Q

What does survival of neurons depend on?

A

Establishing a functional synapse with a muscle cell.

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6
Q

What happens to some neurons even after neuromuscular junctions are made?

A

Some may be eliminated until each muscle fibre is only innervated by one motor neuron.

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7
Q

How are neurons kept alive by their target cells?

A

They release growth factors that keep that axons alive.

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8
Q

Why cannot axons survive if they don’t reach a target cell, when they could survive previously?

A

They need factors from the target cells to stay alive - the factors expressed from the axon at one point are no longer expressed.

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9
Q

What is graded innervation?

A

Within targets there is finer control or to provide more information.

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10
Q

Why is timing important in dependence on target cells?

A

Neurons are not initially dependent on target cells for survival but there is a point in which this “switches” and they become important.

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11
Q

What is important in the timing of dependence of neurons on target cells?

A

Factors in the pathway such as factors from glia or other cells in the pathway - adhesion factors and guidance cues.

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12
Q

What are guidance cues?

A

Signals that tell the axons where to go.

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13
Q

When might cell growth of an axon occur when it has reached the target cell?

A

If the growth factor does not bind to the receptor on the axon.

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14
Q

What is target switching?

A

When during development some neurons must innervate multiple targets/innervate one neuron before another - there is a transitory dependence on a secondary target.

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15
Q

What is haptotaxis?

A

Guidance by adhesive gradients.

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16
Q

What do growth cones express?

A

Cell adhesion molecules that enable them to move by moldulating adhesion to the extracellular matrix and other cells.

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17
Q

What do CAMs recognise?

A

Proteins found in certain basal laminae.

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18
Q

What does laminin do?

A

It paves many axonal tracts, even if only transiently.

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19
Q

What do glycosaminoglycans do?

A

They impede neural outgrowths.

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20
Q

What are homodimers?

A

Molecules that interact with each other.

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21
Q

What are the different locations that CAMs may be found?

A

Sit around the cell membrane, sit in the cell membrane, localised to specific junctions, linked to the cytoskeleton and secondary messenger system.

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22
Q

How do CAMs function if they sit around the cell membrane?

A

They can bind molecules in membranes of neighbouring cells. Examples of these are Ig-CAMs and NCAMs.

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23
Q

How can CAMs function if they are in the cell membrane?

A

They can bind molecules in the extracellular matrix. Examples of these include integrins.

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24
Q

How can CAMS function if they are localised to specific junctions?

A

They can bind proteins in similar junctions on neighbouring cells. Cadherins come under this class.

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25
Q

How can CAMS function if they are linked to the cytoskeleton?

A

They are also linked to a secondary messenger system signalling pathways that will affect cell behaviour such as shape, movement and fate.

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26
Q

What is the main effect of CAMs?

A

Signal to the neuron by secondary messenger systems and links to the cytoskeleton that affect its behaviour and shape.

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27
Q

How many subunits do integrins have?

A

Two.

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28
Q

What is the structure of integrins?

A

Two subunits, expressed on the membrane of the growth cone.

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29
Q

What is the Ig-like domain important for?

A

The interaction between the different parts of the cell adhesion molecules.

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30
Q

What are cadherin molecules?

A

They are more globular like - they contain a domainm within the cell that allows signalling to affect the cell that it is a part of.

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31
Q

What is the structure of the CAM molecules?

A

They are similar in structure to each other - fibronectin domains and ig domains - loop structures that interact with other ig structures in similar molecules.

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32
Q

What are the features of cadherins?

A

They are calcium dependent, transmembrane, homophilic, they act as dimers and they are major components of adherans junctions.

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33
Q

What are the features of the Ig-CAMS?

A

They all express an Ig-rich domain (loop structures so they can interact with other Ig-domains), they are expressed on the cell surface and signal into the cell and allow changes in the cytoskeleton to permit growth in this location.

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34
Q

What are the features of integrins?

A

They are transmembrane proteins that bind adhesive glycoproteins such as fibronectin in the extracellular matrix. They are calcium dependent and recognise an arginine-glycine-aspartate sequence in ECM proteins including vitronectin, fibronectin and laminin. They have several genes.

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35
Q

How are integrins different to other CAMs?

A

They are expressed by the axon but will interact with other molecules in the environment such as proteins expressed in the extracellular matrix. This interaction is calcium dependent.

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36
Q

What is cell adhesion also important in?

A

Keeping groups of axons together.

37
Q

How can cell adhesion interactions be stopped in order to cause divergence?

A

Neural cell adhesion molecules (NCAM) can be polysialylated to stop the homophilic interactions on axons and initiate divergence.

38
Q

What is important for axon pathfinding?

A

It requires adhesion, but without guidance cues nothing would happen.

39
Q

What is the axonal growth cone?

A

A distinct structure that feels the environment - there are dendrites that “feel” the environment to prevent growth to where it is not meant to go.

40
Q

How does the axonal growth cone increase in size?

A

At the front of the growth cone, factors are released that breakdown tissue and allow the axon to make its way through such as proteases.

41
Q

What happens when the growth cone makes contact with the target cells?

A

It will become the termini of the axon.

42
Q

What makes up the main structure of the axon?

A

Tubulin.

43
Q

What is necessary for the body of the axon?

A

Polymerisation of tubulin into microtubules.

44
Q

What do filipodia contain?

A

Actin.

45
Q

What is movement of the growth cone mainly facilitated by?

A

A cytoskeletal lattice containing the motor proteins actin and myosin.

46
Q

What types of guidance cues do neuronal growth cones respond to?

A

Contact mediated and chemotropic guidance cues - the cues ca nbe attractive or repulsive.

47
Q

What kind of ranges can cues act over?

A

Long or short ranges - they may differentially affect particular types of neurons.

48
Q

How is penetration of the tissue by the axon generated?

A

Secretion of proteases that allow the passage of the growth cone.

49
Q

What is a protein highly associated with the growth cone?

A

GAP-43 - role is largely unknown.

50
Q

What does the physical movement of the growth cone require?

A

Polymerisation and breakdown of actin.

51
Q

What does the movement of the axon require?

A

Microtubules.

52
Q

What binds to monomeric actin?

A

Cytochalasins and block polymerisation

53
Q

What binds to polymeric actin?

A

Phalloidin and prevent breakdown.

54
Q

What is the function of cytochalasins and phalloidin?

A

Cytochalasins block polymerisation, phalloidin prevents breakdown of polymerised actin.

55
Q

What are the four guidance mechanisms in axonal pathfinding?

A

Chemorepulsion, chemoattraction, contact repulsion and contact attraction.

56
Q

What are some important evolutionary conserved pathways?

A

Semaphorins, netrins, slits and ephrins.

57
Q

When netrins are secreted, what do they associate with?

A

Cells or the ECM.

58
Q

What is sometimes found with ephrins and semaphorins?

A

They are membrane bound.

59
Q

What can netrins act as?

A

Attractants or repellants.

60
Q

How many receptors are present for each cue?

A

One or more transmembrane receptors.

61
Q

What are semaphorins?

A

A group of around 20 different proteins that are mostly transmembrane.

62
Q

How many semaphorins are secreted?

A

Around 1/3 - positively charged carboxy terminus that increases their affinity for the extracellular matrix.

63
Q

What is significant about the semaphorin domain?

A

It is positively charged and is around 500 amino acids in size.

64
Q

What interaction do semaphorins have with the growth cone?

A

Most repel it.

65
Q

What are plexins?

A

The transmembrane protein receptors for the semaphorin.

66
Q

What is the interaction between semaphorins and plexins?

A

Transmembrane bind directly to plexins whereas secreted semaphorins require an additional protein to bind to the plexin.

67
Q

What is the location of the evolutionary conserved pathways in axonal guidance?

A

Netrins/slits and some semaphorins are secreted and associate with cells/the ECM, ephrins and some semaphorins are membrane bound.

68
Q

What do the different pathways act as, in terms of attractants and repellants?

A

Netrins can act as attractants or repellents whereas slits, semaphorins and ephrins act mostly as repellents, but also attractants in some cases.

69
Q

How are receptors involved in the axonal guidance pathways?

A

There is more than one receptor for each cue that may alter the properties - such as causing the, to be attractants or repellents.

70
Q

How do semaphorins have dual function?

A

They can have an attraction of repulsion effect depending on the other molecules of the environment.

71
Q

Give an example of the dual function of semaphorins.

A

In the presence of NGF Sema III, there is a repellent effect on neurite growth whereas in the presence of NT3, Sema III elicits outgrowth of neurites.

72
Q

What are the characteristics of Slit proteins?

A

The are large, secreted proteins. In mammals there are three slit proteins.

73
Q

What are slit proteins associated with?

A

Repulsion mediated by receptors of the SAX3/Robo family and they signal into the cell to bring about changes that affect the polymerisation of actin.

74
Q

What is the rough size of slits?

A

190kDa.

75
Q

What repeats do slits contain?

A

Leucine-rich repeats and epidermal growth factor-like repeats.

76
Q

What do slits have a role in?

A

Axon guidance at the midline.

77
Q

What axons express Robo (the receptor for slits)?

A

Axons that navigate the midline and prevent them from crossing.

78
Q

What are the characteristics of Robo expressing axons?

A

They run longitudinally and never cross the midline.

79
Q

What is significant about Robo in commissural and non-commissural axons?

A

In non-commisural axons, neither will cross the midline regardless of Robo whereas in Commissural axons, if Robo is downregulated the axons cannot cross whereas they can if Robo is upregulated.

80
Q

What are the characteristics of netrins?

A

They are diffusable proteins that can mediate either repulsion or attraction. They show strong homology to a region of the ECM molecule laminin-1.

81
Q

What are attractive netrins mediated by?

A

Receptors of the DCC/UNC-40 family of receptors.

82
Q

What are repulsive netrins mediated by?

A

The UNC-5 family of receptors.

83
Q

What happens if netrin is knocked out?

A

There is abnormal migration of commissural neurons.

84
Q

What are the different classes of ephrins?

A

Class A and Class B.

85
Q

What are class A ephrins tethered to?

A

The cell surface by a GPI linkage.

86
Q

What are Class B ephrins tethered to?

A

The cell surface by transmembrane domains.

87
Q

What is required by ephrins in order to activate their receptors?

A

They must be clustered.

88
Q

What are ephrin receptors?

A

RTKs that bind specifically to either Class A or B ephrins.

89
Q

What do ephA receptors bind?

A

They bind and activate Ephexin which is a GEF for rho family of GTPases.

BB20028 (7 decks)

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