Tissues 3: Extracellular matrix biology I

Question 1

Define Extracellular Matrix

Answer 1

The ECM is a complex network of proteins and carbohydrates deposited by cells which form the insoluble part of the extracellular environment.

Question 2

List the functions of the Extracellular Environment

Answer 2

Provides physical support

Determines the mechanical and physicochemcial properties of the tissue

Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts

Essential for development, tissue function and organogenesis

PIED

Question 3

Explain the relationship between ECM and Connective tissue

Answer 3

Connective Tissue= extracellular matrix + component cells Connective tissues are tissues rich in ECM add pic

Question 4

List the major components of the ECM

Answer 4

Collagens, Multi-adhesive glycoproteins and Proteoglycans

Question 5

Recall examples of human disorders resulting from ECM pathology which are due to gene mutations affecting the matrix proteins

Include the proteins that are affected by the disease

Answer 5

osteogenesis imperfecta - Type I collagen

Marfan’s syndrome - Fibrillin 1

Alport’s syndrome - Type IV collagen

Epidermolysis Bullosa - Laminin 5 (in all 3 chains) Congenital

Muscular Dystrophy- Laminin 2 (2 chain)

Question 6

What protein is effected by osteogenesis imperfecta

Answer 6

Type I collagen

Question 7

What protein is effected by Marfans syndrome

Answer 7

Marfan’s syndrome - Fibrillin 1

Question 8

What protein is effected by Alports syndrome

Answer 8

Type IV collagen

Question 9

What protein is effected by Epidermolysis Bullosa?

Answer 9

Laminin 5 (in all 3 chains) add pic

Question 10

What protein is effectedd by Congenital Muscular Dystrophy?

Answer 10

Laminin 2 (alpha 2 chain)

Question 11

Recall examples of human disorders resulting from ECM pathology which are due to gene mutations affecting ECM catabolism.

Include the proteins that is effected by the disease.

Answer 11

Hurler’s syndrome - L-alpha-iduronidase add pic

Question 12

List examples of Fibrotic disorders due to excessive ECM depositin

Answer 12

Liver fibrosis - cirrhosis Kidney fibrosis - diabetic nephropathy Lung fibrosis - silicosis

Question 13

Name an example of a disorders due to excessive loss of ECM

Answer 13

osteoarthritis

Question 14

What is collagen composed of an what is its structure

Answer 14

Each collagen molecule comprises three alpha chains, forming a triple helix.

Question 15

How many different alpha chains are the following types of collagen made up off? Type 1 Type 2 Type 3

Answer 15

Type I collagen has chains from two different genes -pro-alpha1(I) chain and also with a pro-alpha2(I) chain Types II and III collagen have only one chain type –

Question 16

What amino acid occupies every third position in a collagen triple helix

Answer 16

Glycine

Question 17

Why does Glycine occupy the 3rd position in a collagen triple helix

Answer 17

every third position must be occupied by glycine, as this is the only amino acid small enough to occupy the interior.

Question 18

What is the molecular composition (what amino acids make up collagen) and structure of collagen?

Answer 18

Characteristic gly-x-y repeat: x is often proline, y is often hydroxyproline Left handed triple helix add pic

Question 19

Explain the biosynthesis of collagen

Answer 19

1) Synthesis of PRO- alpha chain 2)Hydroxylation of Selected Prolines and Lysines 3) Glycosylation of Selected Hydroxylysines 4)Self-Assembly of Three PRO- alpha chains 5) Procollagen Triple-Helix Formation 6) Secretion 7) Clevage of Propeptides 8) Self -Assembly into Fibril add pic

Question 20

What happens to lysine and proline during collagen synthesis

Answer 20

Hydroxylation

Question 21

Why does proline and lysine get hydroxylated

Answer 21

Contributes to interchain hydrogen bond formation. - increase tensile strength

Question 22

What role does Vitamen C play in Callogen synthesis and what effect does a lack of vitamen C cause?

Answer 22

Prolyl and lysyl hydroxylases require Fe2+ and vitamin C Vitamin C-deficiency results in underhydroxylated collagens, with dramatic consequences for tissue stability (scurvy). add pic

Question 23

Name a non-fibrillar type of collagen

Answer 23

Type IV collagen

Question 24

Where is type IV collgen found?

Answer 24

Basement Membrane Type IV collagen is a network-forming collagen and is present in all basement membranes, though its molecular constitution varies from tissue to tissue. add pic

Question 25

What is collagen important for?

Answer 25

Important for tensile stength of tissue

Question 26

Define elastic fibres

Answer 26

elastic fibres are important for the elasticity of tissues

Question 27

What is the composition of elastic fibres

Answer 27

Elastic fibres consist of a core made up of the protein elastin, and microfibrils, which are rich in the protein fibrillin. add pic

Question 28

Name a disorder of elastic fibres and why is it a disorder of elastic fibres?

Answer 28

Marfan’s syndrome Marfan syndrome is a mutation in fibrilin-1 which is a part of microfibrils

Question 29

Define Basement Membrane

Answer 29

Basement membranes (BMs; also called basal laminae) are flexible, thin mats of extracellular matrix underlying epithelial sheets and tubes

Question 30

What is the main components of the Basement membrane?

Answer 30

Collagen type IV Laminins

Question 31

Name the functions of basement membrane

Answer 31

Separation of cells from underlying connective tissue.

In the kidney glomerulus, the BM acts as a highly selective filter. add pic