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The peripheral domain of growth cones is filled with filamentous actin (F-actin). Polymerization of monomeric actin into filaments is what drives the protrusion of the leading edge of the growth cone. At the same time, actin polymers continuously move backward in a rearward flow from the leading edge in the central domain of the growth cone.

In the central domain, F-actin depolymerizes at the same rate as it polymerizes at the leading edge, thus providing a continuous supply of monomers for polymerization at the leading edge. This cycle of polymerization at the leading edge, rearward flow, and depolymerization in the central domain is called treadmilling.

Actin treadmilling alone cannot generate tension to move the body of the growth cone forward.

What else is needed to translate actin polymerization driven membrane protrusion into growth cone advancement?

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Additional push. This is achieved by microtubule polymerization and action of motor proteins associated with the microtubules.


Clutch mechanism. This is achieved by linking F-actin on the inside to the extracellular matrix on the outside.


Differential adhesion. The growth cone forms the strongest adhesive contacts with the extracellular matrix at the leading edge, while adhesion at the trailing edge is weaker.


Pull mechanism. Air pumps found at the leading edge of growth cones create a vacuum into which it gets pulled.

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