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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
How can CAMS function if they are linked to the cytoskeleton?
They are also linked to a secondary messenger system signalling pathways that will affect cell behaviour such as shape, movement and fate.
26
What is the main effect of CAMs?
Signal to the neuron by secondary messenger systems and links to the cytoskeleton that affect its behaviour and shape.
27
How many subunits do integrins have?
Two.
28
What is the structure of integrins?
Two subunits, expressed on the membrane of the growth cone.
29
What is the Ig-like domain important for?
The interaction between the different parts of the cell adhesion molecules.
30
What are cadherin molecules?
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.
31
What is the structure of the CAM molecules?
They are similar in structure to each other - fibronectin domains and ig domains - loop structures that interact with other ig structures in similar molecules.
32
What are the features of cadherins?
They are calcium dependent, transmembrane, homophilic, they act as dimers and they are major components of adherans junctions.
33
What are the features of the Ig-CAMS?
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.
34
What are the features of integrins?
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.
35
How are integrins different to other CAMs?
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.
36
What is cell adhesion also important in?
Keeping groups of axons together.
37
How can cell adhesion interactions be stopped in order to cause divergence?
Neural cell adhesion molecules (NCAM) can be polysialylated to stop the homophilic interactions on axons and initiate divergence.
38
What is important for axon pathfinding?
It requires adhesion, but without guidance cues nothing would happen.
39
What is the axonal growth cone?
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
How does the axonal growth cone increase in size?
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
What happens when the growth cone makes contact with the target cells?
It will become the termini of the axon.
42
What makes up the main structure of the axon?
Tubulin.
43
What is necessary for the body of the axon?
Polymerisation of tubulin into microtubules.
44
What do filipodia contain?
Actin.
45
What is movement of the growth cone mainly facilitated by?
A cytoskeletal lattice containing the motor proteins actin and myosin.
46
What types of guidance cues do neuronal growth cones respond to?
Contact mediated and chemotropic guidance cues - the cues ca nbe attractive or repulsive.
47
What kind of ranges can cues act over?
Long or short ranges - they may differentially affect particular types of neurons.
48
How is penetration of the tissue by the axon generated?
Secretion of proteases that allow the passage of the growth cone.
49
What is a protein highly associated with the growth cone?
GAP-43 - role is largely unknown.
50
What does the physical movement of the growth cone require?
Polymerisation and breakdown of actin.
51
What does the movement of the axon require?
Microtubules.
52
What binds to monomeric actin?
Cytochalasins and block polymerisation
53
What binds to polymeric actin?
Phalloidin and prevent breakdown.
54
What is the function of cytochalasins and phalloidin?
Cytochalasins block polymerisation, phalloidin prevents breakdown of polymerised actin.
55
What are the four guidance mechanisms in axonal pathfinding?
Chemorepulsion, chemoattraction, contact repulsion and contact attraction.
56
What are some important evolutionary conserved pathways?
Semaphorins, netrins, slits and ephrins.
57
When netrins are secreted, what do they associate with?
Cells or the ECM.
58
What is sometimes found with ephrins and semaphorins?
They are membrane bound.
59
What can netrins act as?
Attractants or repellants.
60
How many receptors are present for each cue?
One or more transmembrane receptors.
61
What are semaphorins?
A group of around 20 different proteins that are mostly transmembrane.
62
How many semaphorins are secreted?
Around 1/3 - positively charged carboxy terminus that increases their affinity for the extracellular matrix.
63
What is significant about the semaphorin domain?
It is positively charged and is around 500 amino acids in size.
64
What interaction do semaphorins have with the growth cone?
Most repel it.
65
What are plexins?
The transmembrane protein receptors for the semaphorin.
66
What is the interaction between semaphorins and plexins?
Transmembrane bind directly to plexins whereas secreted semaphorins require an additional protein to bind to the plexin.
67
What is the location of the evolutionary conserved pathways in axonal guidance?
Netrins/slits and some semaphorins are secreted and associate with cells/the ECM, ephrins and some semaphorins are membrane bound.
68
What do the different pathways act as, in terms of attractants and repellants?
Netrins can act as attractants or repellents whereas slits, semaphorins and ephrins act mostly as repellents, but also attractants in some cases.
69
How are receptors involved in the axonal guidance pathways?
There is more than one receptor for each cue that may alter the properties - such as causing the, to be attractants or repellents.
70
How do semaphorins have dual function?
They can have an attraction of repulsion effect depending on the other molecules of the environment.
71
Give an example of the dual function of semaphorins.
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
What are the characteristics of Slit proteins?
The are large, secreted proteins. In mammals there are three slit proteins.
73
What are slit proteins associated with?
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
What is the rough size of slits?
190kDa.
75
What repeats do slits contain?
Leucine-rich repeats and epidermal growth factor-like repeats.
76
What do slits have a role in?
Axon guidance at the midline.
77
What axons express Robo (the receptor for slits)?
Axons that navigate the midline and prevent them from crossing.
78
What are the characteristics of Robo expressing axons?
They run longitudinally and never cross the midline.
79
What is significant about Robo in commissural and non-commissural axons?
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
What are the characteristics of netrins?
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
What are attractive netrins mediated by?
Receptors of the DCC/UNC-40 family of receptors.
82
What are repulsive netrins mediated by?
The UNC-5 family of receptors.
83
What happens if netrin is knocked out?
There is abnormal migration of commissural neurons.
84
What are the different classes of ephrins?
Class A and Class B.
85
What are class A ephrins tethered to?
The cell surface by a GPI linkage.
86
What are Class B ephrins tethered to?
The cell surface by transmembrane domains.
87
What is required by ephrins in order to activate their receptors?
They must be clustered.
88
What are ephrin receptors?
RTKs that bind specifically to either Class A or B ephrins.
89
What do ephA receptors bind?
They bind and activate Ephexin which is a GEF for rho family of GTPases.

BB20028 (7 decks)

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