Regulation of Cell Motility

Question 1

What are the changes that occur in the cells that occur during tumour progression?

Answer 1

Genetic alterations lead to hyperproliferation, disassembly of cell-cell contacts, loss of polarity, increased motility and cleavage of ECM proteins

Question 2

What are the 5 different types of tumour cell migration?

Answer 2

Single cell migration (ameboid) 
Mesenchymal single cells  
Mesenchymal chains  
Clusters/cohorts 
Multicellular strands/sheets

Question 3

What physiological phenomena does tumour migration mimic?

Answer 3

Morphogenesis e.g. angiogenesis

Question 4

What did a comparison of the expression profile of invasive cells vs primary tumours show to be upregulated in invasive cells?

Answer 4

Cytoskeleton regulation

Motility machinery

Question 5

What makes normal migrating cells stop moving?

How are tumour cells different in this aspect?

Answer 5

Contact inhibition of locomotion

They lose contact inhibition of locomotion so they can multilayer

Question 6

What is another term for ECM proteins?

Answer 6

Substratum

Question 7

What are filopodia? What do they do?

Answer 7

Finger-like protrusions rich in actin filaments

Sense the local environment

Question 8

What are lamellipodia?

Answer 8

Sheet-like protrusions rich in actin filaments

Question 9

What are the four main stages of cell movement?

Answer 9

Extension
Adhesion
Translocation
De-adhesion

Question 10

What are the attachments between the cell and the surface that it is moving along called?

Answer 10

Focal adhesions

Question 11

What are the monomers of actin filaments?

Answer 11

G-actin

Question 12

Describe the polarity of acting filaments.

Answer 12

They have a plus end and a minus end

Monomers preferentially get added on at the plus end

Question 13

What protein complex is important in initiating polymerisation?

Answer 13

Arp2/3

Forms a trimer with actin and is good at initiating polymerisation

Question 14

What is the limiting step in actin dynamics?

Answer 14

Formation of Arp2/3-actin trimers to initiate polymerisation

Question 15

State two proteins that bind to free G-actin and describe how they affect elongation.

Answer 15

Promote elongation: profilin (deliver G-actin to the growing filament)
Sequesters G-actin: beta4 thymosin, ADF/ cofilin

Question 16

Name 3 + end capping proteins.

Answer 16

CapZ
Gelsolin
Fragmin/severin

Question 17

Name 2 – end capping proteins.

Answer 17

Tropomodulin

Arp2/3

Question 18

Name 3 severing proteins.

Answer 18

Gelsolin
ADF/ Cofilin
Framin/severin

Question 19

What are the features of the actin filaments in severed populations?

Answer 19

Actin filaments can grow and shrink more rapidly

Question 20

What can happen to single filaments of actin to improve their structural integrity?

Answer 20

They can be bundled or cross-linked

Question 21

Name 6 proteins involved in cross linking and bundling of actin

Answer 21

Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin

Question 22

Which protein allows branching of the actin filaments?

Answer 22

Arp2/3

Question 23

At what angle do actin filaments branch?

Answer 23

70 degree

Question 24

Summarise the actions of Arp2/3.

Answer 24

Initiate nucleation
Cap filaments
Cause branching

Question 25

Describe what causes the gel-sol transition.

Answer 25

Actin filaments can be severed to make the cell more fluid

Question 26

Describe the actin processes that take place during the protusion of lamellipodia.

Answer 26

There is polymerisation, disassembly, branching and capping There is net filament assembly at the leading edge

Question 27

Describe the actin processes that take place during the formation of filopodia.

Answer 27

Actin polymerisation Bundling and cross-linking (NO branching) As soon as the finger wants to retract it will collapse at the base

Question 28

State four signalling mechanisms that regulate the actin cytoskeleton.

Answer 28

Ion flux changes Phosphoinositide signalling Kinases/phosphatases Small GTPases

Question 29

What are the three most important small GTPases in terms of the actin cytoskeleton and what does activation of each cause?

Answer 29

Cdc42 – filopodia Rac – lamellipodia Rho – stress fibres NOTE: these are all part of the Rho family

Question 30

Explain how Rac causes actin polymerisation/organisation.

Answer 30

Rac binds to and activates WAVE | WAVE activates Arp2/3, which is important in actin organisation

Question 31

Explain how Cdc42 causes actin polymerisation/organisation.

Answer 31

Cdc42 binds to WASP | WASP activates Arp2/3

Question 32

Which small GTPases are involved in lamellipodia protrusion?

Answer 32

Rac

Question 33

Which small GTPases are involved in focal adhesion assembly?

Answer 33

Rac and Rho

Question 34

Which small GTPases are involved in contraction?

Answer 34

Rho (stress fibres are important for contraction)