ECM

Question 1

Structural components of ECM

Answer 1

Collagen fibers, elastin, fibronectin

Question 2

Major protein component of ECM

Answer 2

Collagen

Question 3

Collagen structure

Answer 3

Tropocollagen - right handed triple helix
Gly, pro, hydroxypro
3 aa per turn

Question 4

Fibrillar collagen

Answer 4

Type I
Provide tensile strength to skin, tendons, and ligaments
Many overlapping triple helices, covalently linked

Question 5

Non fibrillar collagen

Answer 5

Type IV
Interrupted triple helical domains
Interact with fibrillar collagen to make a network

Question 6

Collagen synthesis

Answer 6

1. Preprocollagen with signal sequence is taken to the ER
2. Remove the sequence and it’s now procollagen
3. ER modifies it
4. Disulfide links will trigger it to become tropocollagen
5. Tropocollagen is taken to the Golgi
6. Tropocollagen is converted into mature collagen via proteolysis
7. Mature collagen can cross link to form insoluble collagen fibrils

Question 7

Defects in collagen synthesis

Answer 7

Scurvy - deficiency in vit c will lead to defective collagen synth
Osteogenesis imperfecta - change in aa sequence of collagen

Question 8

Elastin

Answer 8

Elastic fibers in blood vessels, lungs, ligaments, and skin

Single protein with little post translational sorting

Question 9

Desmosomes

Answer 9

Elastin cross linked 2 D lattice work that confers stretchiness based on modified aa sequence

Question 10

Modified aa in elastin

Answer 10

Lysine to allysine

Question 11

Fibronectin

Answer 11

Attachment point for other cellular components
Cell adhesion, migration, and embryonic development
Tissue and temporally specific

Question 12

Proteoglycans

Answer 12

Ground substance (cement)
Mostly carbohydrate
Carb side chains are polyanionic

Question 13

Difference between glycoproteins and proteoglycans

Answer 13

Proteoglycans - more than 95% sugar, link galactose, unbranched, repeating dimer

Glycoproteins - 70% or less sugar, link mannose, branched, more variety in sugar

Question 14

Major GAGs of ECM

Answer 14

Hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate

Question 15

Synthesis of proteoglycans

Answer 15

Golgi

Disruption leads to mucopolysaccharidosis

Question 16

Degradation of proteoglycans

Answer 16

Lysosomes

Defects lead to mucopolysaccharidosis

Question 17

Role of proteoglycans

Answer 17

Structural support to tissues like cartilage and CT

Question 18

Aggrecan

Answer 18

Large accumulation of proteoglycans

Question 19

Significance of highly negatively charged proteoglycans

Answer 19

Creates osmotic gradient and influx of water to the ECM causing swelling and stiffness making the ECM rigid, flexible, and compressible

Question 20

Hyaluronic acid

Answer 20

Only GAG with no protein core and no sulfation
Longest
Synovial fluid, vitreous humor, cartilage and skin

Question 21

Chondroitin sulfate

Answer 21

Most common GAG

Major component of cartilage

Question 22

Dermatan sulfate

Answer 22

Highest charge density

Similar structure to chondroitin

Question 23

Heparan sulfate

Answer 23

Highest charged
Basement membranes
Anticoagulant

Question 24

Keratan sulfate

Answer 24

Most heterogeneous
3 classes
  I - cornea and cornea hydration
  II - skeletal tissue and bone cartilage
  III - brain

Question 25

Matrix metalloproteases

Answer 25

Proteins that digest other ECM proteins outside the cell

Question 26

Metal cofactor in MMPs

Answer 26

Zinc

Question 27

3 domains of an mmp

Answer 27

Propeptide, catalytic, haemopexin (c terminal that is sometimes not in an mmp)

Question 28

How do you activate a zymogen MMp?

Answer 28

The propeptide domain with the cysteine switch must be removed

Question 29

Once the cysteine switch is removed from the mmp, how can it then break down proteins?

Answer 29

Zinc will activate water molecules which will then react with the amide bond of the protein substrate causing proteolysis

Question 30

Enamelysin

Answer 30

Degrades amelogenin | Amelogenesis imperfecta

Question 31

2 proteins involved in ECM signaling

Answer 31

Integrins, cytokines, growth factors

Question 32

Integrins

Answer 32

Link ECM to cytoskeleton Activate cellular transcription factors leading to gene expression modification Act bidirectionally and can transmit into out of cell to affect things in the ECM

Question 33

Structure of Integrins

Answer 33

Dimer (alpha and beta subu) with divalent cations

Question 34

Cytokines

Answer 34

Manage and manipulate cell responses Involved in inflammatory processes Interleukins and interferons

Question 35

Growth factors

Answer 35

Stimulate cell growth, proliferation and differentiation

Question 36

Functions of ECM

Answer 36

Shape and structure Lubrication and cushioning Anchor for cell adhesion Communication and control life cycles