Cell Adhesion and the Extracellular Matrix

Question 1

What are GAGs?

Answer 1

Glycosaminoglycans

Question 2

When organised by specific proteins, what do GAGs produce?

Answer 2

Glycosaminoglycans, when organised by special proteins, produce proteoglycans

Question 3

What six types of cells are usually found in connective tissue?

Answer 3

1- Fibroblasts
2- Myofibroblasts
3- Chondroblasts
4- Osteoblasts
5- Adipocytes
6- Blood cells

Question 4

What are the two main components of ECM?

Answer 4

1- Fibrillar proteins

2- Polysaccharide glycosaminoglycans (GAGs) which form proteoglycans

Question 5

What are four examples of fibrillar proteins?

Answer 5

1- Collagen
2- Elastin
3- Fibronectin
4- Laminin

Question 6

What is the role of fibroblasts?

Answer 6

Synthesise collagen, elastin and proteoglycans

Question 7

Where is collagen synthesised?

Answer 7

RER of fibroblast

Question 8

What is the precursor to collagen?

Answer 8

Precollagen then tropocollagen

Question 9

What does collagen need to form a triple helix?

Answer 9

1- Vitamin C

2- Supplied -OH in order to allow for triple helix to form

Question 10

How is precollagen made into tropocollagen?

Answer 10

Precollagen is released into the ECM and cleaved to form tropocollagen. Extremely insoluble.

Question 11

What is the solubility of tropocollagen?

Answer 11

Extremely insoluble

Question 12

How is tropocollagen made into collagen?

Answer 12

Aggregation of tropocollagen via enzyme-catalysed cross-linking, making a fibril

Question 13

Describe the process of collagen secretion.

Answer 13

1- Collagen is packaged into large, specialised vesicles in the RER
2- Collagen secretion occurs by exocytosis at specialised sites
3- Collagen is organised and collagen fibrin is produced in a membrane tube called fibripositor

Question 14

In regards to surrounding tendons, how are fibroblasts oriented?

Answer 14

They are oriented along tendon direction in groups so that collagen produced is correctly oriented (parallelism of tendon)

Question 15

Where is elastin produced?

Answer 15

1- Fibroblasts
2- Smooth muscle cells
3- Chondroblasts

Question 16

Where is elastin usually found?

Answer 16

In places it needs to stretch, e.g. aorta, as it has a tendency to stretch and recoil

Question 17

What are proteoglycans an assemblage of?

Answer 17

GAGs and proteins

Question 18

What are the roles of proteoglycans?

Answer 18

1- Matrix support, cushioning and hydration
2- Glue-like function for adhesion
3- Links between ECM proteins, ECM and cell surgace

Question 19

Describe the structure of GAGs.

Answer 19

1- Long chains of repeating disaccharide units
2- Highly negatively charged
3- Highly hydrated

Question 20

What is hyalyuronic acid?

Answer 20

A repeating dissacharide in GAG

Question 21

How is ECM linked to cytoskeleton?

Answer 21

1- Collagen or proteoglycan

2- These bind fibroconectin, which links to integrins, which in turn bind via adatorss to the actin cytoskeleton

Question 22

What are the roles of myofibroblasts?

Answer 22

1- Secrete collagen (fibroblast-like)

2- Synthesise actin, myosin and desmin (smooth-muscle like)

Question 23

What do granules in mast cells contain?

Answer 23

1- Heparin

2- Histamine

Question 24

How are myofibroblasts involved in tissue damage?

Answer 24

1- Prolerate
2- Secrete collagen which helps form a scaffold
3- Consolidate damaged area by forming a fibrous scar
4- Contract to reduce the size of damaged area, thus expressing focal adhesions and smooth muscle actin

Question 25

What is the main role of plasma cells?

Answer 25

Producing antibodies through the secretory pathway

Question 26

What is the main role of macrophages?

Answer 26

Ingesting Listeria bacteria/paramecium

Question 27

What are the main roles of adipocytes?

Answer 27

1- Insulation 2- Packing 3- Storing energy

Question 28

What is the ob gene?

Answer 28

1- Mutant gene 2- Leads to excessive eating 3- Obesity is induced 4- 'Deleted' by leptin

Question 29

What provides the satiety signal?

Answer 29

Leptin

Question 30

What happens to leptin levels in obese patients?

Answer 30

Increases due to decreased sensitivity/increased resistance

Question 31

What are the roles of tight junctions?

Answer 31

1- Define polarity 2- Control passage of substances between cells 3- Link to actin cytoskeleton

Question 32

What is the role of tight junctions?

Answer 32

Plaque anchors actin filaments at the membrane

Question 33

What are the four main types of cadherins?

Answer 33

1- E-cadherin 2- N-cadherin 3- P-cadherin 4- VE-cadherin

Question 34

Where are E-cadherins usually found

Answer 34

Epithelia

Question 35

Where are N-cadherins usually found?

Answer 35

1- Neurons | 2- Heart muscle

Question 36

Where are P-cadherins usually found?

Answer 36

1- Placenta | 2- Epidermis

Question 37

Where are VE-cadherins usually found?

Answer 37

Endothelial cells

Question 38

What is the role of desmosomes?

Answer 38

Linking between strong intermediate filaments and adjacent cells

Question 39

What are the two main structural components of desmosomes?

Answer 39

1- Plaque | 2- Filaments

Question 40

What are the roles of gap junctions?

Answer 40

1- Communication 2- Hydrophobic channel 3- Allow passage of small molecules 4- Coordinate function

Question 41

What are the roles of focal adhesions?

Answer 41

1- Link ECM with cell cytoskeleton 2- Ac as signalling platforms 3- Link to fibronectin

Question 42

How do focal adhesions link the ECM with cell cytoskeletons?

Answer 42

Link ECM through integrins with actin filaments of the cytoskeleton

Question 43

What are the roles of hemidesmosomes?

Answer 43

1- Link ECM to cell cytoskeleton | 2- Link to laminin in basement membrane

Question 44

How do hemidesmosomes link the ECM with cell cytoskeletons?

Answer 44

Link ECM though integrins to intermediate filaments of cytoskeleton

Question 45

What are integrins?

Answer 45

Large family of proteins which bridge between the cell cytosol and ECM

Question 46

Give two examples of integrins.

Answer 46

1- Fibronectin | 2- Laminin

Question 47

What is Duchenne's Muscular Dystrophy?

Answer 47

``` 1- A gene mutation which leads to the absence of dystrophin (adaptor) due to the premature termination of translation 2- Leads to damage to muscle fibre 3- Muscle wasting 4- Muscle weakness 5- Unable to walk by 12 years of age ```

Question 48

What is the cause of Duchenne's Muscular Dystrophy?

Answer 48

Gene mutation which leads to the absence of dystrophin (adaptor) due to the premature termination of translation

Question 49

What is PTC 124?

Answer 49

1- Also called ataluren 2- Experimental druh 3- May override premature stop signal mutation and lead to normal production of dystrophin

Question 50

What are the three steps of cell adhesion in cancer stages?

Answer 50

1- Carcinoma in situ 2- Microinvasion 3- Progression to metastasis

Question 51

Define carcinoma in situ.

Answer 51

1- Tumour cells accumulate to cells' mutations disregulating the normal cell cycle 2- Cells have yet not breached basement membrane

Question 52

What happens during microinvasion?

Answer 52

1- Expression of cadherins is reduced, leading to the cells converting to 'mesenchymal' cells 2- Microinvasion begins and is aided by the secretion of metalloproteases 3- Basement membrane is breached 4- In invading tumours, cells express integrin to promote interaction with ECM and non-epithelial cells during movement

Question 53

What happens in progression to metastasis?

Answer 53

1- Autocrine motility factors are secreted thus increasing motility 2- Angiogenesis factors such as VEGFs are secreted thus promoting vascularisation 3- Metastising tumour enters into lymphatic and blood circulations 4- Invasive carcinoma