Extracellular Matrix Biology II

Question 1

Give two examples of multi-adhesive glycoproteins.

Answer 1

Fibronectin, Laminin

Question 2

Where are Laminins found?

Answer 2

Basement Membrane

Question 3

Describe, in full, the structure of Laminin.

Answer 3

• It is a cross shaped molecule consisting of an alpha, beta and gamma chain
• each end chain has an amino group that beta/ gamma bind to other molecules and alpha binds to integrins
• The N terminus of all the chains there are globular regions
• There is a coiled-coil region, which is the region in which the three chains are wrapped around each other

Question 4

What causes congenital muscular dystrophy?

symptoms

Answer 4

Absence of alpha 2 chain in laminin 2

generalized weakness and join deformities

Question 5

Why is fibronectin considered essential for life?

Answer 5

There are no known mutations of fibronectin in humans

Question 6

Describe three roles of fibronectin.

Answer 6

CONNECTIVE TISSUE

• binding to integrin and linking ECM to the actin
• cytoskeleton – cell binding
• Binding to other ECM components
• helps wound healing by promoting blood clotting

Question 7

What is the general structure of fibronectin?

Answer 7

It is a dimer that is joined by disulfide bonds – it has various domains that can bind to different things

Question 8

Describe the link between fibronectin and the intracellular compartment.

Answer 8

Fibronectin associated with an integrin which associates with actin – forms a mechanical continuum with the actin cytoskeleton
The fibronectin is also bound to collagen

Question 9

What part of fibronectin do integrins bind to?

Answer 9

RGD motif

Question 10

Describe the general structure of proteoglycans.

Answer 10

Consists of a core protein with one or more GAG chains covalently attached

Question 11

What is the basic structure of GAG chains and what is a characteristic feature of GAG chains?

Answer 11

It is a long, unbranched chain consisting of a repeating disaccharide (amino sugar)
It has a large volume
Can form hydrated gels

Question 12

What are the four families of GAG chains?

Answer 12

Hyaluronan
Heparan Sulfate
Chondroitin Sulfate/Dermatan sulphate
Keratan sulfate

Question 13

What is unique about hyaluronan?

Answer 13

It doesn’t have a core protein – it is just a massive polysaccharide
it is carboxylated
It is synthesised on the cell membrane rather than by the ER

Question 14

How are GAG chains linked to the core protein?

Answer 14

It is connected via a link tetrasaccharide

Question 15

What does Decorin do?

Answer 15

Regulates collagen fibre size and arrangement

Question 16

What does hyaline cartilage consist of?

Answer 16

Aggrecan aggregates – consists of aggrecan

needed to cushion the ends of bones

Question 17

Describe how hyaline cartilage resists compressive force.

Answer 17

• The GAG chains in aggrecan are heavily sulphated and carboxylated so it is very negatively charged
• This means that it can attract osmotically active cations such as Na+ and Ca2+, which attracts water forming a gel like substance
• When it experiences a compressive force, the water is squeezed out and the water returns when the compressive force is removed

Question 18

What causes osteoarthritis?

Answer 18

Loss of extracellular matrix

Question 19

What happens in fibrotic disorders?

Answer 19

Excess deposition of collagen – normal tissue gets replaced by collagen