Growth Cones Flashcards

1
Q

How does a neuron grow

A

As it extends, it leaves behind a cytoplasmic trail (axon)

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2
Q

Growth cone defined by cajal

A

Club/battering ram
Endowed by chemical sensitivity which makes it able to arrive to its destination

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3
Q

What are the functions of the growth cone

A

-sensor and motor for axon growth
-perceives and responds to signals in the environment
-Provides motile force for axon and neurite extension
-aids target recognition

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4
Q

How is axon growth directed (what do they prefer?)

A

Growth cones prefer more adhesive substances

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5
Q

What are the substances growth cones show preference for

A

Laminin
Polylysine

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6
Q

How is axon growth directed

A

By diffusible molecules (netrin) which is an attractive cue for axons
Axons grow towards cues

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7
Q

Long range cues examples

A

Chemorepulsion (slit netrins)
Chemoattraction (netrin)

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8
Q

Example of short range cues

A

Contact repulsion (semaphorins,ephrins)
Contact attraction (IgCAMs)

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9
Q

Two dynamic structures in growth cones

A

Filopodia (actin filaments)
Lamellipodia (actin mesh)

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10
Q

What does the central core of the growth cone contain

A

Microtubules
Mitochondria

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11
Q

What are the three regions of the growth cones

A

Central region (microtubule rich)
Transitional region
Peripheral region (F-actin)

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12
Q

What are lamellipodia and filopodia made up of

A

Dynamic bundles of actin and tubulin which continuously polymerise and depolymerise

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13
Q

What is axon treadmilling

A

Actin added to top, removed from the bottom

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14
Q

3 approaches to understand growth cone migration

A

Genetic
In vivo/biochemical
Visualisation

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15
Q

Genetic approach to understand growth cone migration

A

Identify mutations that disrupt axon growth using c elegans and drosophila

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16
Q

In vivo/biochemical approaches

A

Primary cultures of neurons (hippocampal/cortical/retinal)
Add cytoskeletal modifiers

17
Q

Visualisation approaches

A

GFP labelled molecules to visualized growth cone migration

18
Q

Role of growth cone

A

Directs axonal outgrowth

19
Q

Where is the growth cone steered towards

A

Filopodia dilation occurs where the is a greater concentration of diffusable cue, there is more polymerisation

20
Q

Actin polymerisation and depolymerisation

A

Actin added to + (barbed end)
Actin removed from - (pointed end)
Retrograde flow of actin monomers

21
Q

Microtubule polymerisation and depolymerise

A

Tubulin added at + end
Tubulin removed from - end

22
Q

How does net extension occur

A

Polymerisation is greater than disassembly

23
Q

Role of actin depolymerising drugs

A

Slows axonal extension
Prevent growth cone turning

24
Q

What does growth cone turning require

A

Microtubule polymerisation
Engorging filopodium forms the new axon segment

25
What do microtubules polymerise into
Filopodia where actin filaments have been stabilised
26
What are microtubule associated proteins
TIP proteins for monomer addition (APC/CLASP/EB3) Destabilizing proteins (Kif 2A, C/SCG10) Motors (kinesins and dynein) Severing proteins (spastin/ katanin) Stabilizing proteins (MAP1b/Tau/DCX)
27
What causes microtubule invasion of filopodia
Proteins that bind to actin filaments and microtubules
28
What does growth cone progression require
Myosin and interaction with matrix via cell adhesion proteins (CAM/SAM) - which allows adhesion and movement
29
How do growth cones detect cues
Receptors on their surface detect guidance factors e.g. netrin/slit
30
Example growth cone receptors
Robo (changes as growth cone extends)
31
Stages in protrusion
Tip complex activation - bundled actin polymerisation resulting in filopodial extension Actin capping - creation of dendritic network for protrusion Actin severing - new barbed ends for growth
32
Stages in retraction
Actin bundle and network loss - inactivation of barbed end protractor proteins, inactivation of bundling proteins , severing without polymerisation, retrograde actin flow maintained Microtubule shrinkage/destabilization- increased catastrophe, decreased rescue
33
Cytosketal regulators which direct growth cone navigation
Guidance cues and receptors Primary responder molecules Integration (G proteins) Coordination Cytoskeletal effectors Effect
34
Role of GAPs
Rho GTP (active) —-> rho GDP (inactive)
35
Role of GEFs
Rho GDP (inactive) —-> Rho GTP (active)
36
Robo (roundabout) mutant
Axons in wrong direction