Invasion - Regulation of Cell Migration

Question 1

: Most human tumours are derived from X tissues

Answer 1

Epithelial

Question 2

2 types of cell migration?

Answer 2

• Individual cell migration

- Collective cell migration- group of cells which maintain cell-cell contacts

Question 3

What is needed uniquely for collective cell migration regarding cell adhesion

Answer 3

• Cadherins and gap junctions are needed for collective migration

Question 4

Examples of times cells need to move? (3)

Answer 4

organogenesis and morphogenesis, or in wound healing

Question 5

What are the usual stimuli for cell movement (2)

Answer 5

growth factors or chemoattractants

Question 6

How does the morphology of a cell change when they are stimulated to migrate

Answer 6

retraction at the back of the cell and protrusions appear at the front- this helps the cell to move efficiently

Question 7

What stop cells moving and guides them in the right direction

Answer 7

Contact inhibition

Question 8

What specialized structures allow efficient movement (3)

Answer 8

focal adhesions, lamellae, filopodium

Question 9

What are focal adhesions

Answer 9

Points where the cell can hook on to ECM proteins

Question 10

Points where the cell can hook on to ECM proteins are known as …

Answer 10

focal adhesions

Question 11

What protein facilitates hooking of the cell to ECM proteins

Answer 11

Integrins

Question 12

What ends at the point of focal adhesions

Answer 12

Actin filaments

Question 13

Tracks of actin filaments end at …

Answer 13

focal adhesions

Question 14

What are integrins

Answer 14

are transmembrane protein dimers with a short cytoplasmic tail with docking sites for cytoskeletal proteins

Question 15

What are filopodia (consist of (2)… shape…)

Answer 15

Finger-like protrusions rich in actin filaments (and vinculin)

Question 16

What do filopodia do

Answer 16

• They allow cells to sense their environment and coordinate their movement

Question 17

What are lamellipodia (consist of … shape…)

Answer 17

Sheet-like protrusions rich in actin filaments

Question 18

What do lamellipodia do (how do they facilitate movement)

Answer 18

• Sheets project to the front and then ruffle back to allow the cell to move

Question 19

2 types of motility? (regarding cause of movement)

Answer 19

MOTILITY can be HAPOPTATIC (random) or CHEMOTATIC (has purpose e.g. responding to growth factor etc.)

Question 20

4 stages of cell movement?

Answer 20

1. Extension
2. Adhesion
3. Translocation
4. De-adhesion

Question 21

2 types of actin

Answer 21

G and F actin

Question 22

Difference between G and F actin

Answer 22

• G actin (small and soluble) and F actin which is polymerized G actin. F actin is also polar

Question 23

What is the polymerised filamentous form of actin known as

Answer 23

F actin

Question 24

Filaments are X (have different structures in one end compared to the other)

Answer 24

Polarised

Question 25

organisation of F actin in filopodium?

Answer 25

Bundles of parallel filaments

Question 26

organisation of F actin in stress fibres?

Answer 26

antiparallel contractile structures

Question 27

organisation of F actin in lamellipodium?

Answer 27

Branched and cross linked filaments

Question 28

What three structures can actin filaments form

Answer 28

Lamellipodium, filopodium and stress fibres

Question 29

What is the rate limiting step in the organisation of the cytoskeleton

Answer 29

Nucleation

Question 30

What does nucleation of actin achieve

Answer 30

formation of trimers to initiate polymerization

Question 31

What proteins are need for nucleation? what complex does this form

Answer 31

- Arp2 and Arp3 form ARP complexes

Question 32

How does ARP complex interact with actin (which end does it bind to)

Answer 32

- These bind to actin monomers and will be bound at the –ve end of the filament when it has formed

Question 33

What proteins facilitate elongation of filaments

Answer 33

- Prolifin

Question 34

What does prolifin do (which end)

Answer 34

- Prolifin is a protein that binds to actin monomers (G-actin) and brings them to the actin filament to the +ve end to elongate it

Question 35

What does thymosin do

Answer 35

- Thymosin is a protein that binds to actin monomers but doesn’t bring them to the actin filament -> Inhibit the polymerization process

Question 36

What do sequestering protein beta4thymosin and ADF/cofilin do

Answer 36

- Sequestering proteins called beta4-thymosin and ADF/cofilin bind to monomers but do not inhibit polymerization

Question 37

What protein inhibits the elongation of actin filaments

Answer 37

- Thymosin is a protein that binds to actin monomers but doesn’t bring them to the actin filament Inhibit the polymerization process

Question 38

What proteins sequester actin monomers

Answer 38

- Sequestering proteins called 4-thymosin and ADF/cofilin bind to monomers but do not inhibit polymerization

Question 39

What do capping proteins do

Answer 39

- Capping proteins regulate the elongation process of the filaments

Question 40

What is MoA of capping proteins

Answer 40

- They bind to the end of the filament and prevent monomers binding - After a capping protein binds to one end, you get disassembly of some of the filament which causes shortening of the filament

Question 41

What capping proteins bind to the negative end of actin filaments (2)

Answer 41

 Tropomodulin |  Arp complex

Question 42

What capping proteins bid to the positive end of actin filaments (3)

Answer 42

 Cap Z  Gelsolin  Fragmin/severin

Question 43

What do severing proteins do

Answer 43

Regulates filament size

Question 44

What happens in unsevered population of actin filaments regarding growth

Answer 44

- In un-severed populations, filaments grow and shrink relatively slowly

Question 45

What happens in severed population of actin filaments regarding growth

Answer 45

- In severed populations, actin filaments grow and shrink more rapidly

Question 46

Example of severing proteins

Answer 46

Gelsolin, ADF/cofilin, fragmin/severin

Question 47

Bundles of parallel filaments describes the structure of ...

Answer 47

Filopodia

Question 48

antiparallel contractile structures describes the structure of ...

Answer 48

Stress fibres

Question 49

Branched and cross linked filaments describes the structure of ...

Answer 49

Lamellipodia

Question 50

What does fascin do

Answer 50

Protein that bundles filaments at a particular distance

Question 51

What does FIMBRIN do

Answer 51

Does the same but at longer distance between filaments

Question 52

What does alpha-ACTININ do

Answer 52

Bundles

Question 53

What does SPECTRIN do

Answer 53

Cross-links filaments at particular angles

Question 54

What does FILAMIN do

Answer 54

Cross-links filaments at particular angles

Question 55

What does DYSTROPHIN do

Answer 55

Cross-links filaments at particular angles.

Question 56

Proteins that bundle?

Answer 56

FASCIN FIMBRIN -ACTININ

Question 57

Proteins that cross link?

Answer 57

SPECTRIN FILAMIN DYSTROPHIN

Question 58

Depending on the width of the gap between filaments, motor proteins can or cannot ........

Answer 58

travel along the actin filaments

Question 59

What is responsible for branching in lamellae

Answer 59

- Arp2 complex

Question 60

What angle does branching occur at

Answer 60

70 degree angles

Question 61

What is gel-sol transition and when does it take place and by what

Answer 61

When the cell needs to move, the membrane will need to flow- in gel form, the actin cytoskeleton is rigid, but in sol form, the filaments are severed to allow flow

Question 62

Which actin modifying processes are involved in filopodia formation

Answer 62

elongation bundling actin assembly

Question 63

Which actin modifying processes are involved in lamellae formation

Answer 63

``` Assembly Elongation Capping Branching Severing ```

Question 64

Signalling mechanisms that regulate actin cytoskeleton

Answer 64

1. Ion flux changes (i.e. intracellular calcium) 2. Phosphoinositide signalling (phospholipid binding) 3. Kinases/phosphatases (phosphorylation cytoskeletal proteins) 4. Signalling cascades via small GTPases

Question 65

What GTPase subfamily regulates the actin cytoskeleton

Answer 65

Rho subfamily

Question 66

What 3 things activate the Rho subfamily

Answer 66

receptor tyrosine kinase, adhesion receptors (integrins cadherins) and signal transduction pathways

Question 67

Which small GTPase causes lamellipodia

Answer 67

Rac

Question 68

What do stress fibres do

Answer 68

Contractile fibres

Question 69

Which small GTPase causes filopodia

Answer 69

Cdc42

Question 70

Which small GTPase causes stress fibres

Answer 70

Rho

Question 71

What does activation of Cdc42 cause the formation of

Answer 71

Filopodia

Question 72

What does activation of Rho cause the formation of

Answer 72

Stress fibres

Question 73

What does activation of Rac cause the formation of

Answer 73

Lamellipodia