Tissues 4 (ECM)

Question 1

What is a laminin?

Answer 1

Ubiquitous basement membrane protein

Question 2

Wha is the structure of Laminin?

Answer 2

• cross shaped molecule consisting of an alpha, beta and gamma chain
• different parts that have different binding capabilities

Question 3

Why is fibronectin considered essential for life?

Answer 3

There are no known mutations of fibronectin in humans

Question 4

What are the 3 roles of fibronectin?

Answer 4

• binding to integrin and linking ECM to the actin cytoskeleton (cell binding)
• self-association
• binding to other ECM components

Question 5

What is the general structure of fibronectin?

Answer 5

• dimer (2 units) joined by disulphide bonds

- has various domains that can bind to different things

Question 6

What is the link between fibronectin and the intracellular compartment?

Answer 6

• fibronectin associated with an integrin which associates with actin
  – forms mechanical continuum with actin cytoskeleton
• fibronectin bound to collagen

Question 7

What part of fibronectin do integrins bind to?

Answer 7

RGD motif

Question 8

What is the general structure of proteoglycans?

Answer 8

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

Question 9

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

Answer 9

• long, unbranched chain consisting of a repeating disaccharide
• large volume
• can form hydrated gels

Question 10

What are the four families of GAG chains?

Answer 10

• Hyaluronan
• Heparan Sulfate
• Chondroitin Sulfate/Dermatan sulphate
• Keratan sulfate

Question 11

What is unique about hyaluronan?

Answer 11

• doesn’t have a core protein (just a massive polysaccharide)
• synthesised on the cell membrane rather than by the ER

Question 12

How are GAG chains linked to the core protein?

Answer 12

It is connected via a link tetrasaccharide

Question 13

What does Decorin do?

Answer 13

• binds to collagen fibres

- regulates fibrillogenesis (collagen fibre size & arrangement)

Question 14

What does hyaline cartilage consist of?

Answer 14

• core protein (aggrecan) linked to hyaluronan with link protein (aggregates)
• aggrecan GAG chains = keratan sulphate and chondroitin sulphate

Question 15

How does hyaline cartilage resists compressive force?

Answer 15

• GAG chains in aggrecan heavily sulphated & carboxylated so very negatively charged
• attracts osmotically active cations (Na+ & Ca2+) which attract water forming a gel like substance
• with compressive force, water squeezed out and returns when force is removed

Question 16

What causes osteoarthritis?

Answer 16

• loss of extracellular matrix

- cartilage that cushions joint compression is lost

Question 17

What happens in fibrotic disorders?

Answer 17

Too much ECM - normal tissue gets replaced by collagen

Question 18

What is a modular architecture of glycoproteins?

Answer 18

Composed of protein domains of 50-200 amino acids

Question 19

What do all 3 laminin chains have in common?

Answer 19

A globular region at the N terminus

Question 20

What is the coiled region of a laminin?

Answer 20

the region in which the three chains are wrapped around each other

Question 21

What does multi-adhesive mean in terms of glycoproteins?

Answer 21

Multifunctional as different regions can bind to different molecules

Question 21

What are the features of fibronectin?

Answer 21

• large
• multi-adhesive
• derived from one gene
• exists in insoluble fibrillation matrix or soluble plasma protein

Question 21

What are the functions of fibronectin?

Answer 21

• regulates cell adhesion & migration in embryogenesis & tissue repair
• promotes blood clotting

Question 22

What is decorin?

Answer 22

• single GAG chain attached

- dermatan sulfate chain

Question 23

What happens to aggrecan in osteoarthritis?

Answer 23

• degrades (cleaved by aggrecanases & metalloproteinases)
• fragments lost in synovial fluid

Question 24

What happens in fibrosis?

Answer 24

Scar tissue replaces normal tissue