Factors Controlling Cell Behaviour

Question 1

What are the two types of external influences?

Answer 1

Chemical and physical

Question 2

What are the chemical external influences on cells?

Answer 2

Hormones
GF
Ion conc
ECM
Nutrients
Dissolved gas conc

Question 3

What are the physical external influences on cells?

Answer 3

Mechanical stress
Temperature
Layout of ECM + other cells (topography)

Question 4

What is anchorage dependence?

Answer 4

The need for cells to adhere to a large area of ECM in order to:
Respond to GF
Proliferate
Produce protein
Determine phenotype 
Survive

Question 5

How do cells bind to the ECM? Describe this receptor

Answer 5

Via integrins - transmembrane alpha beta heterodimer
Head (alpha and beta) binds to ECM ligands
Short tail binds to actin

Question 6

How do integrins know where to bind onto ECM?

Answer 6

They recognise short peptide sequences

Question 7

Name a common peptide sequence found on more than one ECM

Answer 7

RGD sequence (arg-gly-asp)

Question 8

Which integrin binds to RGD?

Answer 8

Alpha 5 beta 1 fibronectin receptor binds to arg-gly-asp

Question 9

What do a cluster of integrin complexes form?

Answer 9

Focal adhesions or hemidesmosomes

Question 10

Give an example of an integrin found in epithelial hemidesmosomes

Answer 10

Alpha 6 beta 4

Question 11

How many combinations of alpha beta integrin chains are known?

Answer 11

20 combinations

Question 12

Name an integrin which binds to endothelial cells

Answer 12

Alpha 2b beta 2 can bind to ICAM-1 on endothelial cells

Question 13

Name an integrin which binds to CD31

Answer 13

Alpha v beta 3 binds to PECAM - 1 (CD31)

Question 14

What do hemidesmosomes bind to?

Answer 14

Intermediate cytoskeletal filament (not main actin)

Question 15

What is outside in signalling?

Answer 15

Info about the surrounding ECM will determine the integrin complexes which bind, and thus the phenotype of the cell

Question 16

What can open up integrins so that other molecules can bind?

Answer 16

Mechanical stress

Question 17

How do integrins signal downstream?

Answer 17

They don’t have intrinsic signalling capacity, but they can recruit proteins.

Question 18

Name two key signalling proteins recruited by integrins and what they do

Answer 18

Focal Adhesion kinase - phosphorylates Src

Src

Question 19

What is inside out signalling?

Answer 19

Signal from inside the cell can influence the confirmational shape of the integrin

Question 20

Describe the conformational change in integrins which increase their affinity for ECM

Answer 20

Legs bent = low affinity

Legs flexed = high affinity

Question 21

Which factors determine cell population?

Answer 21

Contact inhibition

Competition for growth factors (density dependence)

Question 22

What is density dependence?

Answer 22

Competition for growth factors at high densities can limit cell populations

Question 23

What is the significance of anchorage dependence and density dependence?

Answer 23

(Signals from ECM and soluble GF.)

They both converge to promote proliferation. Individually, the activation is weak, but together, the activation is stronger and sustained.

Question 24

Describe the two types of interactions between cells

Answer 24

Short term contact - no cell cell junctions

Long term - cell cell junctions

Question 25

What is contact inhibition of locomotion?

Answer 25

When cells touch each other, they inhibit motility at the contact side and promote motility at the other side, so that the cells don't crawl over each other.

Question 26

Which normal cells usually do not have contact inhibition of locomotion and why?

Answer 26

Epithelial cells, as they usual form monolayers

Question 27

List the cell cell junctions formed between epithelial cells

Answer 27

``` Zonula = continuous belts Macula = discrete spots Tight junctions Adherens Desmosomes Gap junctions ```

Question 28

What is an important link between cell cell adhesion and proliferation?

Answer 28

Beta catenin

Question 29

What are the effects of cell cell adhesion?

Answer 29

Reduced proliferation via inactive MAPK and increased p27KIP1

Question 30

Describe how cytoplasmic beta catenin is associated with junctions

Answer 30

Calcium dependent homophilic cadherin hinds to beta catenin, which binds to alpha catenin, which binds to actin

Question 31

What degrades beta catenin?

Answer 31

APC

Question 32

What happens when APC is inactive?

Answer 32

There's nothing to degrade beta catenin, so it binds to LEF-1 and promotes gene transcription

Question 33

How else can cadherins influence proliferation?

Answer 33

Cluster of cadherins can alter GTPase activation

Question 34

Give examples of GTPases altered by cadherins following cell cell contact

Answer 34

Rac can be activated (actin polymerisation) | Rho can be invited (involved in contraction of cells during movement)

Question 35

What is an important consequence of loss of contact inhibition?

Answer 35

Metastasis

Question 36

Describe the loss of social skills of cells that can lead them to become cancerous

Answer 36

``` Loss of density dependence Loss of contact inhibition of locomotion Loss of anchorage dependence Break down of cell cell contacts No Hayflick limit Expression of telomerase ```

Question 37

What can cancerous cells produce to cleave through basal lamina and ECM?

Answer 37

Matrix metalloproteinases (MMPs)

Question 38

What is the most common origin of cancerous cells?

Answer 38

Epithelial cells

Question 39

What is the main family of GTPases?

Answer 39

Rho family!

Question 40

What signals the formation of filopodia?

Answer 40

Cdc42 | Stretch your legs and get that will you!

Question 41

What controls the formation of lamellipodia and focal adhesions?

Answer 41

Rac

Question 42

What is the main GTPase involved in stress fibres?

Answer 42

Rho | NO I'm stressed!