Growth Cone Development Notes

Growth Cone

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  • Highly mobile structure that continuously extends and retracts, acting as a sensor for axon growth.

  • Enables movement forward by receiving cues from the environment (attractant or repellent).

  • Extending growth cone can detect both surface cues and diffuse cues.

    • This interaction depends on the receptors of the growth cone.

  • Lamelopodia and filopodia are components of the growth cone.

    • Lamelopodia: meshwork of complexes, extends out from the growing growth cone.

    • Filopodia: bundles the axons together.

    • They assess cues differently.

  • Changes over time, continually forming and deforming as its structure changes.

Microtubules (MT)

  • Extend backwards to stabilize the neuron as the growth cone advances, leaving behind the MT.

  • Extend into the actin-rich area.

  • Stable MT.

Actin Filaments

  • Form a network in the filopodia, behind the growth cone.

  • Found in an actin-rich area.

  • Undergo continual polymerization and depolymerization.

Axon Guidance

  • Studied by looking for mutations that disrupt it.

  • Local changes to polymerization and depolymerization steer the growth cone.

  • Growth cone can sense the high point of a gradient.

  • Differential sensitivity allows the growth cone to detect changes in the environment.

  • Positive cue response: increase polymerization in the filopodia and decrease polymerization in the lamellipodia.

  • Localized direction changes occur within the growth cone.

  • Growth cone recognizes stabilized MT, leading to localized changes in the cytoskeleton.

  • These changes enable alterations in the direction of the growth cone.

Control of Polymerization

  • Controlled by promoting the barbed or pointed end.

  • Modifying how molecules are added allows the structure to change.

Cues and Signal Pathways

  • Molecules bind with receptors, sending information to the growth cone to change.

  • Different signal pathways interact with different actin-modifying molecules.

  • Attractive cue: promotes polymerization.

  • Repellant cue: promotes depolymerization.

  • Exposing drugs that disrupt the stabilization network and MT network leads to depolymerization.

Proteins

  • De-stabilizing proteins prevent the addition of a growing axon and promote depolymerization.

  • Short proteins bind to MT to promote MT polymerization and also sense if there is stabilization in the filopodia.

  • These molecules communicate and coordinate with the extension of the MT network into the region where the MT is stabilized.

  • Promote growth of the MT into regions where the MT have been stabilized, and promote growth of actin filaments behind the stabilized filopodia.

  • Receptors respond to cues from the environment and stabilize the actin and MT network.

Myosin and Actin Interaction

  • Myosin interacts with actin through adhesion molecules interacting between the surface.

  • If anchored, force will allow movement of the actins.

  • Myosin monomers interact with…

Retraction

  • Active when GTP is bound to promote.

  • GDP bound promotes retraction (double check).

Integrated Proteins

  • Different receptors preferentially act on different classes.

  • The integration point allows surveying of the environment to see which cues are predominant and which receptor could respond to it.

  • Identify different domains and see which receptors and proteins they interact with.

  • Promotes either polymerization or depolymerization.