Cell Adhesion

Question 1

How do cells interact with each other?

Answer 1

• tight junctions
• adherens junction
• desmosome
• gap junction
• hemidesmosome

Question 2

What are 3 classifications of cell junctions?

Answer 2

occluding junctions:
- seal epithelial cells together
anchoring junctions:
- mechanically attach cells to their neighbours or to the extracellular matrix
- indirectly linked to the cytoskeleton
communicating junction:
- mediate passage of chemical from one cell to its attached neighbour (gap junctions)

Question 3

What are the different types of anchoring junctions?

Answer 3

• desmosomes (involved in attaching neighbouring cells to each other)
• hemidesmosomes (attach cells to EM)
• adherens junctions (involved in attaching neighbouring cells to each other)
• focal adhesions (attach cells to EM)

Question 4

Which anchoring junctions are linked to the actin cytoskeletons/ actin filament attachment?

Answer 4

• adherens junctions

- focal adhesions

Question 5

Which anchoring junctions are linked to the intermediate filament cytoskeletons/ intermediate filament attachment?

Answer 5

• desmosomes

- hemidesmosomes

Question 6

Why is the indirect attachment of anchoring junctions to cytoskeleton important?

Answer 6

cytoskeleton gives ways to resistant against forces that may burst the cell apart

• much more difficult to pull apart adhesion receptors
• cells that are neighbouring are hard to pull away from each other

Question 7

What are the adherens receptors called in the case of adherens junctions?

Answer 7

Cadherins (dimers)

Question 8

Which type of anchor proteins attach the cadherins to the cytoskeleton actin filaments?

Answer 8

Catenins

Question 9

What are the different types of Catenins?

Answer 9

α-catenin, β-catenin, δ-catenin, γ-catenin

Question 10

What are the functions of Catenins?

Answer 10

• Catenin-cadherin complex - Several types of Catenins work with N-Cadherins to play an important role in learning and memory
• Connecting Cadherins to actin filaments, specifically in these adhesion junctions of epithelial cells
• α-catenin can bind to β-catenin and can also bind actin
• β-catenin binds the cytoplasmic domain of some cadherins

Question 11

What are the intermediate filaments networks composed of in desmosomes?

Answer 11

Keratin

Question 12

What are the adheren receptors called in desmosomes?

Answer 12

• desmoglein & desmocolin

- attached to intermediate filaments in the cytoplasm by adaptor proteins (plakoglobin and desmoplakin)

Question 13

What do hemidesmosomes do?

Answer 13

• Attach cells to extracellular matrix through basal lamina
• Integrin based structures
• Only α6β4 integrin

Question 14

What are Cadherins?

Answer 14

Adhesion receptors
- Calcium dependent molecules (in multiple sites)
○ Critical to function
○ Can be inactive and active
- Always forms a homo dimer
Principle cadherin is (e and n cadherins) (found in epithelial and non epithelial cells)

Question 15

How does Cadherin-mediated adhesion work?

Answer 15

Presence of low levels of Ca
- Not bound to the homo dimer
- Non functional
Addition of Ca to 1mM
- Binding of Ca
- Changing conformation 
- Allows cadherins interact with other cadherins in opposing cells in a zipping like structure

Question 16

How do cadherins help the formation of a neural tube?

Answer 16

Cadherins play a pivotal role in the process:
Tube like structure is forming from a sheet of epithelial cells
1. Invaginations of the epithelial sheet (accompanied by the switching of cadherin expression from E to N)
2. Process continues till it detaches and forms a separate tube
- Process is driven by adherence junctions (especially the interactions with the actin cytoskeleton)
○ The linking of the cells together by the actin cytoskeleton
○ Contracting or relaxing
○ Relaxing in the inside of the bend where invagination is occurring, contraction in the outside of the bend
- Tube formation subsequently occurs due to the detaching

Question 17

Where are E and N cadherins expressed during neural tube development?

Answer 17

E-cadherins are on the outside whereas N-cadherins are on the inside during the invagination

Question 18

What can you notice about E-cadherin expression in the morphology of cancer tumour cells?

Answer 18

• in metastasis, E-cadherin expression looks morphologically similar
• there is a reduced expression of E-cadherin in invasive tumour cells (less cell-cell contact)

Question 19

Why is there reduced expression of E-cadherin in invasive tumour cells compared to primary tissue?

Answer 19

cells in primary tissue undergo epithelial to mesenchymal transition

Question 20

How do cells undergo the epithelial to mesenchymal transition in cancer?

Answer 20

1. Tumour will grow and become invasive
2. Will detach and migrate through blood supply
3. Leaving blood or lymphatic system through extravasation
4. Form macro metastasis
5. Leading to the formation of large secondary tumours
   - Switches off E cadherins which allows them to detach from the primary tumour
   - Switches E cadherin back on when forming the secondary tumour

Question 21

How does malignant melanoma occur?

Answer 21

Arise from the unconditional proliferation of the melanocytes

• cell migrates from the primary site through cadherin switching
  1. Melanocytes (that divide from crest cells) switch on E cadherins so can attach to neighbouring cells
  2. E to N cadherin switch facilitates spread of melanoma cells
• Switched off E cadherin = no longer held in space
• Switches on N cadherin = allows to interact with other melanoma cells
  
  • can interact with fibro blast and endothelial cells that line capillaries = spread and attach onto other cells