Extracellular matrix

Question 1

What is the extracellular matrix?

Answer 1

Network of macromolecules filling spaces between cells. Made of fibrillar and non-fibrillar componants

Question 2

What collagens are found in connective tissues?

Answer 2

Type I (bone), II (cartilage) III (blood vessels) all fibrillar

Type IV (basement membrane , non-fibrillar)

Question 3

What multi-adhesive glycoproteins are found in connective tissue?

Answer 3

Fibronectin, Fibrinogen

Laminins (basement membrane)

Question 4

Which Proteoglycans are found in connective tissue?

Answer 4

Aggrecan
Versican
Decorin
Perlecan (basement membrane)

Question 5

What does the mutated gene affect to cause Osteogenesis imperfecta?

Answer 5

Type I collagen

Question 6

What does the mutated gene affect to cause Marfan’s Syndrome?

Answer 6

Fibrillin 1

Question 7

What does the mutated gene affect to cause Alport’s syndrome?

Answer 7

Type IV collagen alpha 5

Question 8

What does the mutated gene affect to cause Epidermolysis Bullosa?

Answer 8

Laminin 5, in all 3 chains

Question 9

What does the mutated gene affect to cause Congenital Muscular Dystrophy?

Answer 9

Laminin 2 Alpha 2 chain

Question 10

What is an example of disorder of ECM catabolism?

Answer 10

mucopolysaccarides / GAGs inability to be degraded

Question 11

What is Hurler’s Syndrome?

Answer 11

Mutation which leads to a loss of enzyme L-Alpha-iduronidase.

results in the buildup of large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides) in lysosomes

Question 12

What category of disorders can be caused by excess ECM deposition? Give 3 examples

Answer 12

Fibrotic disorders

Liver fibrosis - Cirrhosis

Kidney Fibrosis - diabetic nephropathy

Lung fibrosis - iodiopathic pulmonary fibrosis (IPF)

Question 13

What disorder is Osteoarthiritis an example of?

Answer 13

Disorders due to excess loss of ECM where it is needed for support

Question 14

Why is there a wide variety of connective tissues?

Answer 14

Different types of collagen with various arrangement coupled with or without different ECM components can create diversity

Question 15

What are the characteristics of Diabetic nephropathy? Why does it lead to renal failure?

Answer 15

There is an accumulation of extracellular matrix making thick basement membrane, This restricts renal filtration , so can lead to renal failure

Question 16

What are the characteristics of Alport syndrome?

Answer 16

Mutations in collagen IV resultl in abnormally split GBM which is associated with loss of kidney function and hearing loss.

Question 17

What do elastic fibres consist of?

Answer 17

Protein elastin core and microfibrils which are rich in protein fibrillin surrounding.

Question 18

What disorder is caused by mutations in fibrillin 1 protein?

Answer 18

Marfan’s syndrome

skeletal, ocular and cardiovascular system can be affected. Px can be predisposed to aortic ruptures. Arachnodactyly

Question 19

In the protein Elastin, what are the two segments that alternate along the polypeptide chain?

Answer 19

Hydrophobic regions and alpha helical regions rich in alanine and lysine. many of the lysine side chains are covalently cross linked

Question 20

What makes ECM proteins multi-adhesive?

Answer 20

Their modular architecture. ie, They are made of protein domains of 50-200 amino acids. Makes them multifunctional and can bind to various components /receptors

Question 21

What are the structural characteristics of laminins?

Answer 21

Heterortrimeric proteins made of alpha, beta, gamma chains. Form cross shaped molecules. Large proteins

Each chain molecular weight 160-400kDa

Question 22

How do Laminins act as multi-adhesive proteins?

Answer 22

can interact with receptors Integrins and Dystroglycan.
Can self-associate with basement membrane matrix as well as other matrix components : type IV collagen, Nidogen, proteoglycan

Question 23

Diseases such as muscular dystrophy, epidermolysis bullosa, congenital muscular dystrophy arise from what?

Answer 23

Absence of alpha 2 chain in laminin 2. Symptoms include hypotonia, weakness and deformities of the joints

Question 24

Extracellular matrix extra info?

Answer 24

• key functions : physical support, mechanical and physiochemical properties of the tissue, influences the growth, adhesion and differentiation of cells and tissues it interacts with, essential for development tissue function and organgenesis

cells found in connective tissues : fibroblast, macrophage, basal lamina, collagen fibre, mast cell, elastic fibre, capillary, glycosaminoglycans, proteoglycans, glycoproteins

• properties of connective tissues ( tendon and skin = tough and flexible ) ( bone - hard and dense ) ( cartilage = resilient and shock absorbing )