Extracellular Matrix (ECM)

Question 1

What is the difference between collagens and elastin?

Answer 1

While both are structural proteins, collagens impart strength and elastin gives resilience.

Question 2

What is a glycosaminoglycan (GAG)?

Answer 2

A complex sugar that binds water and resists compression

Question 3

What’s a proteoglycan?

Answer 3

Protein covalently bound to a glycosaminoglycan

Question 4

Name and describe the three layers of the basement membrane.

Answer 4

Lamina lucida (e- poor region, appears lighter in color), lamina densa (e- rich region, appears darker in color), and lamina reticularis (underneath lamina densa and fuses with the stroma)

Question 5

What type of cells make up the laminina lucida? Lamina densa?

Answer 5

1. Epithelial
2. Epithelial
   Note that they make the bulk of the basement membrane.

Question 6

How consistent is stroma size among cells?

Answer 6

It isn’t. Stroma size is greater in liver and almost non existent in bone (bone is almost entirely ECM).

Question 7

Describe collagen. What’s it’s repeating structure”?

Answer 7

1. Provides strength to tissues. Is stretch resistent

2. Repeating structure = Gly-X-Y, where X and Y = Lysine and Proline (usually) to be -OH’ed for fibril making purposes

Question 8

What types of collagen are fibril making collagens? What are their functions

Answer 8

A. Type I: bone, skin, tendons, ligaments (osteogenesis imperfecta)
B. Type II: cartilage (trhis plus Type II and Type IX make aggrecan. (chondrodisplasia)
C. Type III: Skin and blood vessels (Ehler-Danlos Syndrome-Anurism

Question 9

How to make fibril-forming collagens

Answer 9

1. Translate collagen into RER (will need SRP protein to get there, but remove it once it reaches SER)
2. Vitamin C adds OH’s to it. Without it, you get SCURVY DISEASE (teeth fall out)
3. Triple helix forms.
4. Extension peptides are cleaved
5. Collagen enters golgi for secretory pathway
6. The peptide extensions are cleaved post-secretion (tropocollagen). Self assembles into large fibril. STRIATED
   Note: If you lose a Gly, you will get a weaker structure

Question 10

Describe fibril-associated collagen

Answer 10

It is of the Type IX variant of collagen. It decorates the fibrils, and a mutation here leads to epiphyseal dysplasia , causing arthritis in the joints. NOT STRIATED. Extension peptides are theoretically not cut off here (but the formative said they were…)

Question 11

Describe network-forming collagen.

Answer 11

It comes from Type IV collagen. Extension pepetides are kept on to interact with N and C termini. Multilayered, and NO STRIATIONS.

Question 12

Describe type XVII collagen

Answer 12

It makes anchoring collagen, linking epithelial cells to the lamina lucida.

Question 13

Describe Type VII collage

Answer 13

It is found in the stroma and connects from the lumina densa into connective tissue. It personally interacts with the fibrils.

Question 14

What happens if Type VII collage screws up?

Answer 14

You would lose the ability to anchor onto the fibril, leading to blistering below the basal membrane. (Lamina densa separation = epidermopolysis bullosa = epithelium + basement membrane splitting)

Question 15

What happens if type XVII stops functioning properly?

Answer 15

There will be a separation between the epithelium and the lamina lucida.

Question 16

Describe elastin in detail

Answer 16

It is strechable, assembled outside of the cell like collagen, provides tissue resilience, is used to make fibrils and microfibrils, and is interspersed with collagen fibers.

Question 17

What happens if something goes wrong with elastin?

Answer 17

Marfan syndfrome (Fibrillin 1 mutation leading to extended arms and legs because of failed recoil development. It also leaves the AORTA prone to rupturing.

Question 18

What happens if Type III collagen is mutated?

Answer 18

You develop hyperextendable skin, and are prone to aneurysms.

Question 19

What happens if elastin is mutated?

Answer 19

Can lead to elastoderma disease (reduced recoiling of the skin)

Question 20

Describe glycosaminoglycans (GAG)

Answer 20

It is a repeating disaccharide where the aminosugar is sulfated and uronic acid acts as a carboxylic acid (NEGATIVE CHARGE!!! at pH 7). BINDS TO FLUID (joints, eye humor…)

Question 21

What is hyaluronic acid?

Answer 21

A GAG that’s non-sulfated (so can’t bind to proteins)

Question 22

What’s chondroitin sulfate? Heparan sulfate?

Answer 22

Both are GAGs (sulfated) which bind proteins. This + Type IV yieled Perlecan, found in the basal lamina

Question 23

What is chondroitin sulfate used for?

Answer 23

Syndecan 1 compoenent. Found in fibroblasts and epithelial surface. It has a transmembrane comain and INTERACTS WITH CYTOSKELETON

Question 24

What does Heparan sulfate bind to in the ECM?

Answer 24

On ECM side of Syndecan, binds to growth factors for Syndecan.

Question 25

What is Laminin?

Answer 25

Uses Alpha, beta, and gamma chains. It’s an adhesive glycoprotein that binds proteoglycans. It’s the major part of the basal lamina. Can bind integrins

Question 26

Describe fibronectin

Answer 26

Uses RGD amino acid sequence. Binds proteins and proteoglycans.

Question 27

Describe integrins

Answer 27

Works as a dimer. Binds extracellularly, uses RGD sequence. Beta subunit binds to cytoskeleton inside cell.

Question 28

Name the different Beta units of integrins

Answer 28

Beta 1 binds ECM
Beta 2 = in leukocytes
Beta 3 = in platelets
Beta 4 = in hemidesmosomes

Question 29

What happens if you mess with beta 2 integrins?

Answer 29

Leukocytes would not be able to slow down due to lack of adhesion. So it would not be able to fall through endothelium. NO LEUKOCYTE EXTRAVASATION

Question 30

What happens if beta 3 suffers?

Answer 30

You gey Glansmann’s disease, where platelerts can’t bind fibrinogen during clotting.

Question 31

Integrin molecules are always active (T/F)

Answer 31

F: they are super regulated (activated by a signal receptor before ECM component can bind to anything) to prevent unnecessary clotting and leukocyte entry.

Question 32

How does the cytoplasmic domain of integrin work?

Answer 32

It must first be triggered by the ECM domain. IN other words, ECM signal binds to signal receptor, which activated the ECM component of the integrin.