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Flashcards in Axon Guidance Deck (51)
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What are growth cones?

The motile sensory tips of growing axons

(and dendrites for that matter)


What is a neurite?

A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete


What are the features of growth cones on neurites?

Highly dynamic and motile

They explore the environment seeking guidance cues

They form focal contacts with the substrate that provide a tensile grip in which to establish process elongation. 



Describe the cytoskeleton in growing axons


. To change direction an axon must be able to rapidly dismantle its cytoskeleton in one orientation in favour of its establishment in another direction.


Describe the microtubules in growing axons

Filamentous protein polymerised to form tensile cables - forms the backbone of the nerve process

- can also be referred to as intermediate filaments


What is the function of actin in the neurites?

Filamentous protein on the extremity of the growth cones


What is the activity of the microtubules in the growth cone?

The growth cone is the factory in which axon microtubules are stabilised or destabilised, and they in turn respond to interactions with actin, the filamentous proteins of the growth cone extremity.


What are the three arbritrary zones of the growth cone?

The central or core region

Transition region

Peripheral region



What happens in the transitional region of growth cones?

This is where most of the microtubule actin interactions take place


What is the peripheral region largely composed of?

Actin filaments


What are the states that actin can exist?

As a monomer

Diffuse network of polymerised actin filaments


They can also be polarised to form rigid filaments that form the backbones of thin processes that protrude from the growth cone body


What are filopodia?

Slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells.


What do filodopia contain?

They contain actin filaments cross-linked into bundles by actin-binding proteins, e.g. fascin and fimbrin.


What is the purpose of filodopia?

Filopodia form focal adhesions with the substratum linking it to the cell surface


Define lamellipodia

The lamellipodium (plural lamellipodia) (from Latin lamina, "thin sheet"; pod, "foot") is a cytoskeletal protein actin projection on the leading edge of the cell


What doe lamellipodia contain?

It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate.


It is the re-organisation of these actin structures that lays down the path to be taken by the growing axon, and this path is established by subsequent stabilization of microtubules in the orientation dictated by actin filament assembly and consolidation. 





Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia


What are actin filaments composed of?

Bundled actin monomers bound to ATP or ADP molecules


Why is ATP actin preferentially added to the distal end of an actin filament?

ATP-actin and ADP-actin can be bound or released at either end, but the equilibrium constant for ATP-dissociation is greater at the pointed (proximal) end, and so ATP-actin is preferentially added to the barbed (distal) end of an actin filament.


Pointed = proximal

Barbed = distal


When does treadmilling occur?

In the absence of acin binding proteins


What is treadmilling?

ATP-actin is added at the barbed end, hydrolysed rapidly to ADP-Pi-actin and then the phosphate group is slowly dissociated to ADP-actin, which can be released from the pointed end.


What is the significance of the equilibrium between actin polymerisation and depolymerisation?

The equilibrium between actin polymerisation and depolymerisation is the driving force behind axon elongation and retraction


What are microtubules composed of?

Microtubules are also polarised structures made up of repeating units of a-tubulin and b-tubulin dimers.


Which dimers add to the distal end and which dimers add to the proximal end?

a/GTP-b-tubulin dimers add to at the distal end and a/GDP-b-tubulin dimers dissociate from the proximal end


Again, rapid hydrolysis of GTP to GDP occurs within the tubule.


What post-translational modifications might occur to the tubulin as the tubules age and stabilise?

detyrosination or acetylation


What follows in the protrusion of filodopia and lamellopodia which stimulates growth?

Influx of microtubules and organelles



(Termed engorgement)


What is the process of consolidation?

Cell membrane tightens around the newly formed cable of microtubules resulting in consolidation of the nervous process.


What determines the direction of travel of the neurite?

The direction in which these processes occurs is driven by the direction in which the initial filopodial and lamellipodial protrusion takes, which is in turn dictated by environmental signals perceived by membrane receptors on the surface of the growth cone.


Environmental signals - detected by growth cone receptors - lemallipodial and filopodial protrusion


'But the direction in which an axon grows is ultimately determined by the spatial distribution of the environmental signals perceived by the growth cone, or the effect of the environment on distributing key signalling molecules within the growth cone.'


After there is detection of the environmental signal, what prompts the polymerisation and depolymerisation of the cytoskeleton?

transduction of a series of signals largely mediated by the sequential phosphorylation of a chain of intracellular proteins that ultimately impinge on molecules involved in mediating the polymerisation or depolymerisation of the cytoskeleton




What does it mean if the transduction pathways are convergent?

The same downstream signals may be activated by pathways originated by different surface receptors


Different surface receptors result in the activation of the same downstream signals