ECM

Question 1

Network Forming Collagens (2)

Answer 1

Types 4, 7

Question 2

Collagen type 12: type, location, disease

Answer 2

Fibril-Associated with type 1, found in tendons and ligaments, no disease

Question 3

3 GAGs in ECM and their properties

Answer 3

1. Hyaluronic Acid—no sulfate, no attached protein
2. Heparan Sulfate- sulfate attached, protein attached (Membrane bound associated with Syndecan; Extracellular associated with Perlecan)
3. Chondritin Sulfate-sulfate attached, protein attached

Question 4

Laminin

Answer 4

Adhesion Glycoprotein that is the major component of the basal lamina (associated with Integrins a6B1, a7B1, and a6B4)

Question 5

Fibronectin

Answer 5

Adhesion glycoprotein with modular organization (domains with distinct functions)
RGD sequence binds other ECM proteins
Associated with Integrin a5B1

Question 6

Biosynthesis of collagen: which collagens, where does it begin, where does it end, what are the key steps, what cofactor do you need

Answer 6

Involves Collagens 1,2,3,5,11 (fibril forming)
Beings in ER (cotranslational transported there)
Ends in ECM
1. Pro-a chains hydroxylated then glycosylated
2. Assemble with extension peptides
3. 3 chains form triple helix
4. Secreted from cell via sec. Vesicle
5. Extension peptides cleaved
6. Self assembly into fibril
7. Fibril–>collagen fibers

*need Vit C

Question 7

Type 17 Collagen: type, location, disease

Answer 7

Transmembrane collagen, located with hemidesmisomes

Disease=Bullous Pemphigoid

Question 8

Transmembrane Collagens (1)

Answer 8

Type 17 Collagen

Question 9

Collagen type 11: type, location, disease

Answer 9

Fibril forming, associated with type 2, regulates diameter, no disease

Question 10

B2 Integrin mutation

Answer 10

Issue with WBCs stopping (Leukocyte Adhesion Deficiency)

Question 11

Fibril Forming Collagen Types (5)

Answer 11

1, 2, 3, 5, 11

Question 12

Type 4 Collagen: type, location, disease

Answer 12

Network forming Collagen (forms chicken wire sheets), located in basal lamina
No disease
*Does not cleave extension peptides

Question 13

Collagen type 5: type, location, disease

Answer 13

Fibril forming associated with type 1, regulates diameter (no dx)

Question 14

Integrin—–Ligand—Where

6 total

Answer 14

a5B1---Fibronectin---all over
a6B1---Laminin---all over
a7B1---Laminin---muscle 
aLB2---IgSuperfamily---WBC
a2B3---Fibrinogen---platelets 
a6B4---Laminin---Hemidesmisomes (epithelia)

Question 15

Elastin-where assembled, key structural aspects (2), function

Answer 15

Assembled in ECM
Highly cross linked, and made of fibrillin surrounded by microfibrils
Resilience

Question 16

Type 7 Collagen: type, location, disease

Answer 16

Network forming collagen/Anchors fibrils, located between the stratified squamous epithelia
*has disulfide bonds
Disease=Epidermylosis Bullosa (anchoring fibrils disrupted, epithelium and basement membrane pulled apart)

Question 17

3 Main PGs in ECM, main features of each

Answer 17

1. Aggrecan–GAG chain=chondritin sulfate, keratin sulfate; found in cartilage, strength
2. Syndecan–GAG chain=heparan sulfate, chondritin sulfate; found in fibroblasts and epithelial cell surface; binds to FGF ligand (GFs), adhesion
3. Perlecan—GAG chain= heparan sulfate, found in basal lamina, structural and filtering function

Question 18

Collagen type 3: type, location, disease

Answer 18

Fibril-Forming (specifically this forms reticular fibers–special silver stain), located in skin, blood vessels, organs

Disease associated=Ehlers Danlos Syndome/anneurism, hyperextendible skin

Question 19

Collagen Type 9: Type, Location ,Disease

Answer 19

Fibril-Associated, associated with type 2 (cartilage)
Disease=Epiphyseal Dysplasia, joint issues/arthritis
*does not cleave extension peptides

Question 20

Fibril Associated Collagens (2)

Answer 20

Types 9, 12

Question 21

PGs in ECM-function and structure

Answer 21

Function- present GFs to membrane receptors

Structure: Core protein with GAG side chains bound covalently

Question 22

Basement membrane (3 zones in order top to bottom)

Answer 22

TOP 1. Lamina Rara

2. Lamina Densa
3. Lamina Reticularis BOTTOM

Question 23

GAGs in ECM: features (5)

Answer 23

“Glycosaminoglycans”

• neg charge
• osmotically active
• can bind H20
• compressible
• highly extended

Question 24

Elastin diseases (2)

Answer 24

1. Marfarns Syndrome: Mutation in Fibrillin 1–aortic rupture, MV prolapse, very long limbs, lack of recoil
2. Elastoderma: reduced recoil

Question 25

4 Macromolecule Components of ECM

Answer 25

1. Structural Proteins
2. GAGs
3. PGs
4. Adhesive Glycoproteins

Question 26

Integrin B3 Mutation

Answer 26

Can’t bind Fibrinogen during clotting—Glanzmanns Disease

Question 27

Collagen type 2: type, location, disease

Answer 27

Fibril-forming, found in cartilage, Disease=chondroplasia

Question 28

Ninogen

Answer 28

Adhesion Glycoprotein associated with the Lamina Densa

Question 29

Integrins- interaction with ECM and interaction with cytoskeleton

Answer 29

Interact with ECM protein RGD sequence via both subunits
Interact with Cytoskeletal elements (usually actin) via B subunit interacting with actin binding proteins that bind actin

Question 30

2 main types of structural proteins in ECM

Answer 30

1. Collagen

2. Elastin

Question 31

Collagen structural elements (3)

Answer 31

1. Gly-X-Y repeating AA sequence (often Proline, Lysine; to be hydoxylated, deaminated for cross link formation re: fibril formation)
2. Tensile strength, resistance
3. Triple a helix

Question 32

Collagen type 1: type, location, disease

Answer 32

Fibril forming; bone, skin, cartilage, 90% of collagen is this kind
Disease associated: osteogenesis imperfecta

Question 33

Adhesion Glycoproteins in the ECM (3)

Answer 33

1. Fibronectin
2. Laminin
3. Ninogen