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DMD 5243 > ECM > Flashcards

ECM Flashcards

1
Q

Structural components of ECM

A

Collagen fibers, elastin, fibronectin

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2
Q

Major protein component of ECM

A

Collagen

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3
Q

Collagen structure

A

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

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4
Q

Fibrillar collagen

A

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

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5
Q

Non fibrillar collagen

A

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

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6
Q

Collagen synthesis

A
  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
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7
Q

Defects in collagen synthesis

A

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

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8
Q

Elastin

A

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

Single protein with little post translational sorting

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9
Q

Desmosomes

A

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

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10
Q

Modified aa in elastin

A

Lysine to allysine

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11
Q

Fibronectin

A

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

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12
Q

Proteoglycans

A

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

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13
Q

Difference between glycoproteins and proteoglycans

A

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

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

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14
Q

Major GAGs of ECM

A

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

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15
Q

Synthesis of proteoglycans

A

Golgi

Disruption leads to mucopolysaccharidosis

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16
Q

Degradation of proteoglycans

A

Lysosomes

Defects lead to mucopolysaccharidosis

17
Q

Role of proteoglycans

A

Structural support to tissues like cartilage and CT

18
Q

Aggrecan

A

Large accumulation of proteoglycans

19
Q

Significance of highly negatively charged proteoglycans

A

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

20
Q

Hyaluronic acid

A

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

21
Q

Chondroitin sulfate

A

Most common GAG

Major component of cartilage

22
Q

Dermatan sulfate

A

Highest charge density

Similar structure to chondroitin

23
Q

Heparan sulfate

A

Highest charged
Basement membranes
Anticoagulant

24
Q

Keratan sulfate

A 
Most heterogeneous
3 classes
  I - cornea and cornea hydration
  II - skeletal tissue and bone cartilage
  III - brain
25
Q

Matrix metalloproteases

A

Proteins that digest other ECM proteins outside the cell

26
Q

Metal cofactor in MMPs

A

Zinc

27
Q

3 domains of an mmp

A

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

28
Q

How do you activate a zymogen MMp?

A

The propeptide domain with the cysteine switch must be removed

29
Q

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

A

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

30
Q

Enamelysin

A

Degrades amelogenin

Amelogenesis imperfecta

31
Q

2 proteins involved in ECM signaling

A

Integrins, cytokines, growth factors

32
Q

Integrins

A

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

33
Q

Structure of Integrins

A

Dimer (alpha and beta subu) with divalent cations

34
Q

Cytokines

A

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

35
Q

Growth factors

A

Stimulate cell growth, proliferation and differentiation

36
Q

Functions of ECM

A

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

DMD 5243 (11 decks)

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