ecm

Question 1

what are the causes and symptoms of osteogenesis imperfecta?

Answer 1

defective collagen type 1 synthesis
point missense mutation
glycine –> bulkier amino acid
fragile bones, blue sclera, weak tendons, thin skin

Question 2

what is the inheritance pattern of type 1 osteogenesis imperfecta?

Answer 2

autosomal dominant

Question 3

what are the two types of osteogenesis imperfecta and how severe are they?

Answer 3

OI 1 - mildest and most common

OI 2 - very severe, de novo, lethal

Question 4

what causes Marfan’s syndrome?

Answer 4

mutant, misfolded fibrillin which causes elastin to be too stretchy

Question 5

what are the symptoms of Marfans?

Answer 5

tall
long arms and legs
loose joints
floppy cardiac valves
eye problems
aortic aneurysms
spider fingers

Question 6

what is the inheritance pattern of Marfan’s?

Answer 6

autosomal dominant

Question 7

explain the cell migration model

Answer 7

actin filaments polymerise to change the shape of the cel

adhesion proteins attach at the leading edge

detach from trailing edge

Question 8

what happens in cell migration on a flat surface with no ECM?

Answer 8

cell detachment and apoptosis

Question 9

how do cancer cells impact cell migration and the ECM?

Answer 9

cleave cell adhesion molecules
break down ECM
growth factors and cytokines facilitate migration and metastasise

Question 10

what are the functions of the ecm?

Answer 10

• Functions as adhesive substrate
• Provides structure
• Presents growth factors to their receptor
• Stores growth factors
• Senses and transduces mechanical signals

Question 11

what is in ECM/

Answer 11

o Collagens
o Elastin
o Glycoproteins
o Proteoglycans

Question 12

how are macromolecules secreted and how do they change outside of cells?

Answer 12

secreted as small precursors and they polymerise once outside cells

Question 13

describe the structure of collage?

Answer 13

triple helix made up of glycine and either proline or hydroxyproline (every 3rd amino acid is glycine)

Question 14

how much of the total body mass is collagen?

Answer 14

25%

Question 15

how many types of collagen are there?

Answer 15

19

Question 16

what are the 2 main families of collagen?

Answer 16

o Fibril forming – Type I, II and III

o Non-fibrillar – the rest

Question 17

where is type 1 collagen found?

Answer 17

skin
tendon
bone
most loose/dense CT
ligaments

Question 18

where is type 2 collagen found?

Answer 18

hyaline cartilage

Question 19

where is type 3 collagen found?

Answer 19

lymphoid organs

Question 20

where is type 4 collagen found?

Answer 20

basement membrane (along with type 6)

Question 21

what is osteogenesis imperfecta?

Answer 21

brittle bone disease

Question 22

what are the genes affected in type 1 osteogenesis imperfecta?

Answer 22

 Chromosome 17, COL1A1 gene

 Chromosome 7, COL1A2 gene

Question 23

what is the mutation which causes osteogenesis imperfecta type 2?

Answer 23

new mutation - de novo

Question 24

where is elastin found?

Answer 24

blood vessels, lungs, ligaments and dermis of skin

Question 25

what is elastin made of?

Answer 25

glycine proline more valine than collagen

Question 26

why do elastic fibres need fibrillin?

Answer 26

to stop them stretching too far stability helps anchor fibres to other ECM proteins

Question 27

what effect does damage to fibrillin have on TGF-B?

Answer 27

causes more TGF-B to be released into the ECM so fibroblasts make more ECM

Question 28

what are glycoproteins?

Answer 28

proteins with oligosaccharides attached

Question 29

what are the roles of glycoproteins?

Answer 29

o Receptors on cell surface - Bacteria, viruses, toxins, hormones, other cells o Strength and support to the ECM o Slime layer of bacteria and flagella

Question 30

what are the 2 main glycoproteins that help with cell adhesion?

Answer 30

fibronectin | laminin

Question 31

what happens to your preoteoglycans as you get older?

Answer 31

o Smaller protein cores and fewer side chains o Less water held  drier  CT more brittle and more likely to be damaged  less shock absorbency o Seen in IV disc

Question 32

what can cause odema?

Answer 32

increased proteoglycan formation

Question 33

what are the 5 major protein families that cell adhesion molecules belong to?

Answer 33

– Cadherins – interact with similar molecules on the other cell – Ig Super family – interact with similar molecules on the other cell – Selectins - selects and attaches a cell to the ECM – Mucins – will attach to selectins – Integrins – work with fibronectin and laminin

Question 34

describe the basic principles of cell migration on a 2D surface?

Answer 34

- polymerisation of actin filaments at leading edge gives a protrusive force - senses environment as it proves forward - moves in direction of growth factors - new cell adhesion molecules at the front - adhesion molecules detach from the back - • Forces produced by contractile network combined with actin filament and disassembly help to retract the trailing cell edge.

Question 35

describe cell migration on a 3d fibrillary ecm?

Answer 35

* Cell has to force its way through scaffold of collagen and elastin fibres – not unidirectional movement * If ECM is nicely lined up like in dense regular CT, then the cell can just push itself in one direction * If dense irregular or loose CT then its more likely to have an amoeboid movement.

Question 36

what are the steps of leukocyte extravasion?

Answer 36

"chemoattraction", "rolling adhesion", "tight adhesion" and "(endothelial) transmigration" (amoeboid movement through basement membrane to get to ECM).

Question 37

how do cells migrate in cancer?

Answer 37

* Cancer cells produce proteins which break down the cell adhesion molecules. * Loosens cancer cells within the tumour cells, allowing them to break off. * Go through rolling movement and can break down ECM holding cells together. * Degradation of ECM allows invasive cells to migrate into surrounding tissue and vasculature * Activation of growth factors and cytokines increases cell migration and likelihood of metastasis