Lecture 10 Flashcards
Axon guidance
- Neuron migrates to final position to create neurites
- Neurites travel long distances to reach final targets, where each neurite has growth cone
- Have filopodia that interact with intermediate environment
What does axonal transport provide
Supplies to growth cone
- Cell body site of protein synthesis
- Membrane components for growth cone extension made as vesicles transported in growing neurite
- Proteins for neuronal extension transported inside vesicles by anterograde axonal transport
Actin and Tubulin
Movement of filopodia driven by actin filaments
As growth cone moves forward, backbone continually reinforced with microtubules
Growth cone adheres to adjacent cells/ECM
What is axon growth influenced by
Cell adhesion molecules (CAMs)
Substrate adhesion molecules (SAMs)
Diffusible guidance molecules
Structure of growth cone
Central domain - microtubules, organelles, vesicles etc
Transitional zone
Peripheral domain - actin, lamellipodia (flat regions of dense actin between filopodia), filopodia
Actin pushes the cell forward; myosin II pulls it back.
Clutch proteins anchor the actin to the surface.
Microtubules and organelles move forward.
Attractive cues boost movement; repulsive cues inhibit it.
Directional migration is controlled by cue balance.
How does an axon know where to go?
- Growth cone highly motile
- Sensitive to attractive/repellent cues as guideposts
- CAMs/SAMs/diffusible chemotropic molecules give guidance
N-CAM
On surface of neurons/glial cells
Homophilic adhesion via immunoglobulin domains
> 27 isoforms
N-CAM knockout mice shows axon migration defects
N-cadherin
- 5 cadherin repeats
- B-sheet sandwich
- Homophilic calcium ion dependent adhesion
- Functional unit is a dimer
- Anti N-cadherin antibodies prevent outgrowth of Xenopus retinal axons