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 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?

Answer 5

Contact inhibition of locomotion

Question 6

How are tumour cells different in this aspect?

Answer 6

They lose contact inhibition of locomotion so they can multilayer

Question 7

What is another term for ECM proteins?

Answer 7

Substratum

Question 8

What are filopodia?

Answer 8

Finger-like protrusions that are rich in actin filaments

They sense the local environment

Question 9

What are lamellipodia?

Answer 9

Sheet-like protrusions that are rich in actin filaments

Question 10

What are the four main stages of cell movement?

Answer 10

Extension
Adhesion
Translocation
De-adhesion

Question 11

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

Answer 11

Focal adhesions

Question 12

What are the monomers of actin filaments?

Answer 12

G-actin

Question 13

Describe the polarity of acting filaments.

Answer 13

They have a plus end and a minus end

The monomers preferentially get added on at the plus end

Question 14

What protein complex is important in initiating polymerisation?

Answer 14

Arp2/3

This forms a trimer with actin and is good at initiating polymerisation

Question 15

What is the limiting step in actin dynamics?

Answer 15

Formation of Arp2/3-actin trimers to initiate polymerisation

Question 16

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

Answer 16

Promote elongation – profilin (these deliver the G-actin to the growing filament)
Sequesters G-actin addition- thymosin

Question 17

What regulates addition of g actin to polymer

Answer 17

Balance between elongation using profilin and sequestering via thymosin

Question 18

Name some + end capping proteins.

Answer 18

CapZ
Gelsolin
Fragmin/severin

Question 19

Name some – end capping proteins.

Answer 19

Tropomodulin

Arp2/3

Question 20

Name some severing proteins.

Answer 20

Gelsolin ADF
Framin/severin
Cofilin

Question 21

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

Answer 21

Actin filaments can grow and shrink more rapidly

Better if they are unsevered

Question 22

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

Answer 22

They can be bundled or cross-linked

Question 23

Name some proteins involved in actin linking

Answer 23

Alpha-actinin 
Fimbrin 
Filamin 
Spectrin 
Villin 
Vinculin

Question 24

Which protein allows branching of the actin filaments?

Answer 24

Arp2/3

Question 25

At what angle do they branch?

Answer 25

70 degree

Question 26

Summarise the actions of Arp2/3.

Answer 26

They initiate nucleation They cap filaments They cause branching

Question 27

Describe what causes the gel-sol transition.

Answer 27

The actin filaments can be severed to make the cell more fluid

Question 28

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

Answer 28

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

Question 29

Describe the actin processes that take place during the formation of filopodia finger protrusion

Answer 29

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

Question 30

State four signalling mechanisms that regulate the actin cytoskeleton.

Answer 30

Ion flux changes Phosphoinositide signalling Kinases/phosphatases Small GTPases

Question 31

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

Answer 31

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

Question 32

Explain how Rac causes actin polymerisation/organisation.

Answer 32

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

Question 33

Explain how Cdc42 causes actin polymerisation/organisation.

Answer 33

Cdc42 binds to WASP | WASP also activates Arp2/3

Question 34

Which small GTPases are involved in lamellipodia protrusion?

Answer 34

Rac

Question 35

Which small GTPases are involved in focal adhesion assembly?

Answer 35

Rac and Rho

Question 36

Which small GTPases are involved in contraction?

Answer 36

Rho (stress fibres are important for contraction)

Question 38

Important proteins in all types of cell migration

Answer 38

Proteases and integrins

Question 39

Important proteins specific to collective cell migration

Answer 39

Cadherins and gap junctions

Question 40

What changes does cell undergo before migration

Answer 40

Changes shape so normally goes from round to having a leading edge Cells become polarised in half of direction of movement Organelles become polarised in that region

Question 41

Name of large filamentous actin polymer

Answer 41

F-actin

Question 42

What is important process associated with extension during movement

Answer 42

Polymerisation of actin

Question 43

Important process in adhesion during cell movement

Answer 43

Gel/sol transition so cell becomes more flexible

Question 44

Important process in translocation in cell movement

Answer 44

Contraction of actin to move cell along

Question 45

What happens if growth signal factor turns up in opposite direction to travel

Answer 45

Actin is disbanded into g actin and reassembled on other side Note the power of one of these signals