Cell Adhesion 4 - Adhesion on behaviour

Question 1

What is compaction?

Answer 1

• hallmark event of 8 cell stage in mouse embryo developement
• when you can no longer see the intercellular boundaries as adhering junctions form
• E-cadherin is essential for formation of adhering here
• found mainly on basolateral cell-cell contact sites

Question 2

Where is E-cadherin mainly found during compaction?

Answer 2

Basolateral cell-cell contact sites

Question 3

Describe 2 experiments defining cadherin-mediated adhesion

Answer 3

• adhesion-blocking antibodies - exposure to anti-cadherin antibodies causes embryo to fall apart
• expression and deletion of cadherin - mutant embryos lacking E-cadherin fall apart

Question 4

Explain loss and gain of function mutations

Answer 4

• if you remove what you think is causing the effect, does the effect still happen?
• when the feature is back does it function again?

Question 5

name 3 different types of cadherins?

Answer 5

• E-cadherin
• R-cadherin
• Cadherin-6

Question 6

Where is E-cadherin expressed in the embryo?

Answer 6

• mainly in epithelial cells

Question 7

Where is R-cadherin and N-cadherin mainly expressed?

Answer 7

nerve, muscle and lens cells

Question 8

Where is P-cadherin expressed in the embryo?

Answer 8

• placenta
• epidermis

Question 9

Where is Cadherin-6 expressed?

Answer 9

kidney

Question 10

What is homopihilic binding?

Answer 10

• 2 molecules that are identical on different cells bind

Question 11

What is heterophilic binding?

Answer 11

two molecules that are different on different cells bind

Question 12

Explain homophobic binding in cadherin

Answer 12

• happens at the N-terminus - furthest point from the membrane
• Ca2+ is required or hinge would be floppy
• Changes conformation of the N-terminus

Question 13

Explain overall connections of cadherins

Answer 13

• individual interactions are relatively weak
• combination is strong
• important as cell-cell interactions commonly break and re-from during embryonic development

Question 14

What allows cells to sort according to origin

Answer 14

• homophilic binding - cadherins bind well to the same type of cells
• suggests that tissues are maintained by differential affinities of cells for each other

Question 15

What causes tissue maintenance

Answer 15

• cadherins bind well to the same type of cell
• cells have differential affinities for each other

Question 16

What is an L-cell?

Answer 16

cells in the GI tracts that secreted hormones regulating appetite

Question 17

Explain L-cells and cadherins

Answer 17

• they do not normally express cadherins
• can be cultured to express L-cells

Question 18

What does a higher level of catherine expression mean?

Answer 18

• stronger interaction - more tightly packed in the centre

Question 19

What does a lower level of expression of cadherin mean?

Answer 19

• weaker interactions - around the outskirts

Question 20

Explain overall sorting of cells based on their catherine expression

Answer 20

• express different cadherins - will group together into completely different groups
• express different levels of the same cadherin
  - more cadherin in the centre, less catherine in outskirts

Question 21

Explain the expression of cadherins in neural tube development

Answer 21

• ectoderm expressed E-cadherin
• as neural tube starts to form - stop making E-cadherin - start making N-cadherin
• cadherin 6B expressed increases at join between E-cadherin and N-cadherin
• some cells stop making N-cadherin and start making cadherin-7
• neural crest is then formed and more cadherin-7 is made

DRAW IT OUT

Question 22

What is the effect of over expression of N-cadherin in neural tube formation?

Answer 22

• failure to leave the neural tube

Question 23

Name 6 epithelial features

Answer 23

• regular columnar morphology
• high degree of cell adhesion
• cell-cell junctions
• specialised apical membrane (eg brush border)
• underlying basement membrane
• cells relatively static

Question 24

Name 6 mesenchymal features

Answer 24

• irregular rounded or elongate morphology
• loss of apico-basal polarity
• front-back polarity
• dynamic adhesions
• lamellipodia and filopodia
• cells highly motile

Question 25

What are lamellipodia?

Answer 25

- protrusion from migrating cells - lots of actin

Question 26

what are filopodia?

Answer 26

- extensions in migrating cells - made of membrane - sensory function

Question 27

Explain the epithelial-mesenchymal transition (EMT)

Answer 27

- formation of epithelium is reversible - cells can transition from epithelium so mesenchymal cells

Question 28

Explain epithelial-mesenchymal transition in cancer progression

Answer 28

- cancer happens due to an accumulation of mutations in different genes - allows for metastasis - carcinomas are around 80% of all cancer cases - metastasis accounts fro 90% of cancer deaths

Question 29

What is carcinoma?

Answer 29

- cancers arising from epithelial cells

Question 30

What are selections?

Answer 30

- proteins on the cell surface that bind carbohydrates - expressed by white blood cells and epithelial cells (these line the blood vessels) - linked to actin through transmembrane proteins - mediate cell-cell adhesions in the bloodstream

Question 31

Explain the role of selectins in inflammation

Answer 31

- weak binding and rolling of white blood cells along blood vessels - leukocytes activate integrins, which recognise epithelial membrane proteins - stronger adhesion - lymphocyte will escape into the tissues

Question 32

Explain defects in leukocyte adhesion

Answer 32

LAD-I - absent or decreased integrins - defective tight adhesion and invasion LAD-II - glycosylation defect causing selectin defects - defective initial binding and rolling LAD-III - activation defect of integrin - defective tight adhesion and invasion

Question 33

What does LAD stand for?

Answer 33

leukocyte adhesion deficiency

Question 34

What is LAD-I?

Answer 34

absent or decreased integrins - defective tight adhesion and invasion

Question 35

What is LAD-II?

Answer 35

glycosylation defect causing selectin defects - defective initial binding and rolling

Question 36

What is LAD-III?

Answer 36

activation defect of integrin - defective tight adhesion and invasion

Question 37

What is the role of remodelling of the ECM in inflammation?

Answer 37

allows white blood cells tp pass between cells

Question 38

Name the 2 main groups of ECM degrading enzymes

Answer 38

- matrix metalloproteinases (MMPs) -> need Ca2+ or Zn2+ to work - serine proteases -> conserved serine residue on the active site Very specific enzymes

Question 39

Explain localised ECM degradation

Answer 39

- overall ECM structure stays the same - but there is enough room for cells to migrate through

Question 40

Explain localisation of ECM degradation

Answer 40

- some proteases secreted in inactive forms - localised activator converts to be active - tissue plasminogen activator activates plasminogen to dissolve blood clots - some proteases confined by cell-surface receptors - urokinase-type plasminogen activator (uPA) found at the growing tip of migrating cells - some proteases are inhibited by locally secreted inhibitors - tissue inhibitors of metalloproteinases (TIMPs)

Question 41

Explain ECM remodelling in cancer

Answer 41

- carcinoma in situ - basement membrane breakage - proteolytic ECM degradation happens - invasive tumor - tumor spreads