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

in ALL 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.
• It has different parts on the laminin that have different binding capabilities.
• At the N terminus all the chains have Globular Regions.
• There is a coiled-coil domain, where the three chains are wrapped around each other.
• Derived from several genes.

Question 4

What are the features of the Laminins

Answer 4

Very LARGE
Multi-adhesive - different regions of the molecules can bind to different molecules
Interact with cell surface receptors e.g. integrins.

Question 5

What causes congenital muscular dystrophy and what are the symptoms?

Answer 5

Absence of alpha 2 chain in laminin 2.

• Hypotonia
• Generalised weakness
• Deformities of the joints

Question 6

Why is fibronectin considered essential for life?

Answer 6

There are no known mutations of fibronectin in humans

Question 7

Describe 4 roles of fibronectin.

Answer 7

-Binding to Actin cytoskeleton via integrins:
Extracellular region of the integrin binds with fibronectin and the intracellular region links with actin. Fibronectin—-Integrin—actin
-Interacts with other surface molecules and ECM
-Important in regulating cell adhesion, migration in embryogenesis, tissue repair
-Important for wound healing (promotes blood clotting)

Question 8

What is the general structure of fibronectin?

Answer 8

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

Question 9

Describe the link between fibronectin and the intracellular compartment.

Answer 9

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 10

What part of fibronectin do integrins bind to?

Answer 10

integrins bind to fibronectin via RGD molecules which is on the cell binding site. Integrins recognise the RGD motif.

Question 11

What are the 2 forms that fibronectin can exists as and how are there different forms of fibronectin

Answer 11

Can exits as insoluble fibrillar matrix OR soluble plasma protein.
It is derived from one gene- different forms comes from different types of mRNA splicing.

Question 12

Describe the general structure of proteoglycans.

Answer 12

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

Question 13

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

Answer 13

It is a long, unbranched chain consisting of a repeating disaccharide.

• It has a large volume relative to their mass.
• Can form hydrated gels which can be very resistant to compression.
• One of the two sugars in repeating disaccharide is always amino sugar
• Many GAGs are sulfated or carboxylated, which makes it highly negatively charged

Question 14

What are the four families of proteoglycans?

Answer 14

• Hyaluron
• Chondroitin sulfate and dermatan sulfate (Chondroitin sulfate has glucuronic acid instead of iduronic acid) (carboxylate and sulfate which makes it negatively charged)
• Heparan sulfate
• Keratan sulfate

Question 15

What is the structure of hyaluron

Answer 15

Also called hyaluronic acid.

• Hyaluronan is unique in being simply a carbohydrate chain. No core protein (UNIQUE)
• Synthesized at the cell surface, not in the ER/Golgi
• Unsulfated
• A single long chain up to 25,000 repeated disaccharides

Question 16

How are GAG chains linked to the core protein?

Answer 16

It is connected via a link tetrasaccharide

Question 17

What does Decorin do?

Answer 17

Regulates collagen fibre size and arrangement.

Question 18

Describe decorins structure?

Answer 18

• A small proteoglycan with a single dermatan sulfate chain
• Binds to collagen fibres
• Essential for fibre formation.
• regulates collagen fibre size and arrangement.

Question 19

What does hyaline cartilage consist of?

Answer 19

Aggrecan aggregates – consists of aggrecan (GAG chains = keratan sulphate and chondroitin sulphate) associated with hyaluronan and a link protein

Question 20

Describe how hyaline cartilage resists compressive force.

Answer 20

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 21

What causes osteoarthritis?

Answer 21

Excessive loss of ECM. aggrecan gets degraded and the fragments get lost in the synovial fluid.

Question 22

What happens in fibrotic disorders?

Answer 22

Too much ECM production. Normal tissue gets replaced by collagen.
Scar tissue replaces normal tissue
E.g. Liver cirrhosis, lung fibrosis.

Question 23

How do you best describe the structure of fibronectin?

Answer 23

V-shaped molecule composed of two identical chains linked by disulphide bridges

Question 24

How would you best describe proteoglycans?

Answer 24

Long, linear, highly charged polysaccharide covalently linked to protein core