Midterm 2

Question 1

Growth cones

Answer 1

• Integrate environmental cues to generate directed outgrowth
• Motility guided by dynamic cytoskeletal interactions between actin and tubulin-based filaments

Question 2

What are the two ways guidance cues can act to direct growth cones (by alternating cytoskeletal dynamics)?

Answer 2

1. By contact
2. Over long distances

Question 3

Cajal’s Drawings and Initial Inklings

Answer 3

• Drew growth cones and noticed they terminated in swellings
• Inferred that something dynamic was going on, possibly chemically

Question 4

Cajal’s Neurotropic Theory

Answer 4

If neuroblasts have chemotactic properties, they may be capable of ameboid movements.

• Initiated by factors secreted from epithelial, neural, or mesodermal elements
• Processes oriented in direction of chemical gradients and guided to secreting cells

Question 5

Short (Contact) vs. Long Range (Diffusible) Cues

Answer 5

Short:
- Attractive or repulsive to growth cones
- Contact with ECM or other cells
- Mediated by transmembrane receptors because cues typically can’t get through plasma membrane

Long:
- Attractive or repulsive to growth cones
- Cells release diffusible proteins
- Detected by transmembrane receptors

Question 6

Growth Cone Structures (Membrane Elements)

Answer 6

Lamellipodia: Ruffled membrane that senses external cues (like webbing between fingers)

Filopodia: Thin, highly motile membrane extensions that sense external cues

Question 7

Commonalities between lamellipodia and filopodia

Answer 7

1. Highly dynamic (like amoeba)
2. Very sensory (detect cues)

Question 8

Growth Cone Structures (Cytoskeletal Elements)

Answer 8

Axon (main body and growth cone): highly-ordered, parallel microtubules–more directed in one direction

Lamelipodia and filopodia: actin fibers–more sporadic orientation

Question 9

T or F: actin and microtubules have polarity (plus and minus end)

Answer 9

T

Question 10

Actin microfilaments

Answer 10

Strands of actin pairs (dimers), often interacting with strands of other proteins

Question 11

Microtubules

Answer 11

Long, hollow cylinders made of many molecules of tubulin (alpha and beta tubulin)

Question 12

Experimenting with Actin

Answer 12

1. Growth cone exposed to graded concentration of cytochalasin drug

Result: Actin depolymerized on one side, axons turns away from where cytochalasin was added

Takeaway: Messing with actin changes growth direction of axons/growth cones

Question 13

Actin moving inward to center of growth cone

Answer 13

• Actin polymerizes at distal end (near filopodium) by adding actin dimers to this end and bend/severs at proximal end (near center of growth cone)
• Retrograde flow of actin (opposite direction of growth cone movement)
• Actin filaments “treadmill”

Question 14

Extension of Filopodia

Answer 14

• Actin treadmilling extends filopodium (protrusion)
• Transmembrane adhesion molecules connect to actin filaments and attach treadmill to substrate (then, retrograde flow slows and protrusion increases)

Question 15

Growth Cone Turning (entire structure turns toward extending filopodium)

Answer 15

• Pioneering microtubules extend from axon into growth cone, growing along actin filaments
• Attractive cues stabilize actin filaments and extend filopodia
• Microtubules follow extending actin/filopodium and extend the growing axon