10. Cell Motility

Question 1

What is the function of focal adhesions in cell motility?

Answer 1

Act as “hooks” for cells onto surfaces so that they can move forwards in a collective manner

Question 2

How are focal adhesions formed?

Answer 2

Integrin dimer receptors act as hooks, which attach cytoskeletal components via docking sites in their short cytoplasmic domains

Question 3

Which cytoskeletal component is used in focal adhesions?

Answer 3

Filamentous actin = like “muscles of cell”

Question 4

Recall the 3 main peripheral actin structures involved in motility

Answer 4

Lamellipodia
Filopodium
Stress fibres

Question 5

Describe the structure and function of lamellipodia

Answer 5

Structure: stretchy membrane
Function: expands and contracts to move cell forwards

Question 6

Describe the structure and function of folipodia

Answer 6

Structure: Finger-like protrusions
Function: sensory = environmental exploratory

Question 7

Recall the actin arrangement in lamellipodia

Answer 7

Mesh/net-like

Question 8

Recall the actin arrangement in filopodia

Answer 8

Parallel filaments

Question 9

Recall the actin arrangement in stress fibres

Answer 9

Anti-parallel (for contraction)

Question 10

Distinguish G-actin and F-actin

Answer 10

G-actin = monomer
F-actin = polymer

Question 11

Recall the 6 actin-driven processes that need to be controlled

Answer 11

1. Remodelling
2. Elongation
3. Capping
4. Severing
5. Cross-linking/ bundling
6. Branching

Question 12

Distinguish hapoptatic and chemotactic movement

Answer 12

Hapoptatic = aimless non-directional cell movement
Chemotactic = purposeful, polar movement

Question 13

Which family of proteins are involved in regulation of actin remodelling

Answer 13

Arp

Question 14

What is the limiting step in actin remodelling reactions

Answer 14

Trimerisation of monomer before it can polymerise

Question 15

Summarise the control of actin filament elongation

Answer 15

1. Promoted by prolifin which binds to G-actin to transport it onto the end of new filaments
2. Inhibited by thymosin, which competes with prolifin for actin-binding

Question 16

Give examples of 2 proteins that bind to the positive end of actin

Answer 16

CapZ

Severin

Question 17

Give examples of 2 proteins that bind to the negative end of actin

Answer 17

Tropomodulin

Arp

Question 18

What is the function of severing actin filaments?

Answer 18

Allows growth/ shrinking of filaments to be sped up

Question 19

Recall the 3 possible fates of severed actin filaments

Answer 19

1. Barbed ends capped
2. Annealed
3. Added to a new strand

Question 20

Recall 2 proteins involved in control of actin cross-linking and the resulting actin structure

Answer 20

1. Alpha-actinin –> cross linking of parallel strands = like a ladder
   2, Filamin –> V-shaped actin filament

Question 21

Which protein family is involved in controlling actin branching?

Answer 21

Arp complex

Question 22

Recall the family of proteins involved in signalling the development of each different actin structure in locomotion, and which individual protein drives development of each structure

Answer 22

Rho (Subfamily of Ras)
Lamellipodia = Rac
Filopodia = CDC42
Stress fibres = Rho

Question 23

Summarise the process of de-differentiation that leads to production of a benign tumour

Answer 23

1. Disassembly of cell-cell contacts

2. Loss of polarity

Question 24

Summarise the processes that lead to progression of a benign tumour to a malignancy

Answer 24

Invasion of BM
Increased motility
Cleavage of ECM proteins

Question 25

Summarise the process of metastasis

Answer 25

• Metastatic cells become mobile mesenchyme-type cells + enter bloodstream. When they reach new organ = lose their mesenchymal characteristics to form new tumour

Question 26

What are the 2 broad methods of cell migration? Give 2 examples of mechanisms for each of these

Answer 26

1. Single-cell (ameboid movement, mesenchymal)

2. Collective movement (clusters, multicellular strands)

Question 27

Give an example of a cancer type that shows a preference for amyboid movement

Answer 27

Leukaemia

Lymphoma

Question 28

Give an example of a cancer type that shows a preference for collective multicellular strand movement

Answer 28

Glioblastoma

Question 29

What genetic change is often seen in tumours that have lost contact-inhibition?

Answer 29

Upregulation of cytoskeletal regulator and motility machinery genes