cell migration 1

Question 1

Importance of Cell Migration

Answer 1

Cell migration is necessary for development
What are some migratory processes that we’ve discussed so far?

Cell migration is required once development is complete
White blood cells of the immune system (e.g. Chemotaxis: Chemo “chemical”; movement “taxis”)
Cancer metastasis

Cell migration employs signal transduction pathways and proteins shared with many different cellular processes
What might cell migration and endocytosis have in common?

Question 2

How to approach this topic?

Answer 2

Anxiety-inducing because there are many interesting things that we could talk about. So many rabbit trails that one could follow. eg. High-Calcium Concentration Microdomains promote growth cone steering

Question 3

Complex subcellular cytoskeletal events at the growth cone drive cell migration and guidance

Answer 3

EATD;extension, adhesion, translocation, de-adhesion

Extracellular guidance cues signal secondary events within the cell (signal transduction pathways) that direct changes in the cytoskeleton (especially changes in the actin cytoskeleton and microtubules).

The highly dynamic nature of growth cones allows them to respond to the surrounding environment by rapidly changing direction or by branching in response to various stimuli

Constantly ‘searching’ out the environment to allow for changes in directionality in response to cues

Stimuli (extracellular guidance cues) can be attractive or repulsive, initiating changes in the direction of the growth cone by altering the direction of the filipodia and lamellipodia
Achieved by altering the underlying cytoskeleton within the growth cone

Question 4

Growth cones

Answer 4

Highly specialized ends of migrating axons that are rich in cell guidance receptors, cell surface adhesion molecules, cytoskeletal proteins → The responsive regions of the cell involved in migration

Question 5

Actin

Answer 5

Small (42kDa) conserved protein that exists in both globular (monomeric, G-actin) and filamentous (F-actin) form

Question 6

Actin nucleation

Answer 6

(process of making an actin polymer) is controlled by ATP binding

Two parallel F-actin strands must rotate 166 degrees to layer correctly on top of each other

F-actin has a directionality → ATP rich region is the ‘+’ where polymerization, while the “-” end is ADP bound and would be undergoing depolymerization → a constant dynamic instability, is at play (continuous growing and shrinking)

Question 7

four stages of cellular outgrowth

Answer 7

encounter, protrusion, engorgement, and consolidation

Question 8

encounter

Answer 8

Recognize migration cue

Question 9

protrusion

Answer 9

Rapid extension of filopodia and lamellar extensions along the leading edge of the growth cone

Question 10

engorgement

Answer 10

Filopodia move to the lateral edges of the growth cone, and microtubules invade further into the growth cone (creating a stabilizing core to the growth cone → MT are rigid)

Question 11

consolidation

Answer 11

Occurs when the F-actin at the neck of the growth cone depolymerizes and the filopodia retract

Question 12

example of Actin severing proteins

Answer 12

ADF/Cofilin, Actin-depolymerizing factor/Cofilin

Question 13

example of Actin polymerizing proteins

Answer 13

Arp2/3 complex, Actin related protein complex 2/3

Initiates the polymerization of actin daughter filaments at 70° angles to mother filaments

Question 14

WASp/Scar proteins stimulate the formation of new actin filaments by Arp2/3 complex

Answer 14

1. signal activate wassp/scar. arp2/3 complex activatio and filament nucleation. then filament elongate. the plus-end caps. phosphate release. ADF/cofillin binding and unbinding. tropomyosin binds. debranching occurs. depolymeriz and monoer diffsuse and nucleotide exchange.