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DMD 5243 > ECM > Flashcards

Flashcards in ECM Deck (36):
1

Structural components of ECM

Collagen fibers, elastin, fibronectin

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Major protein component of ECM

Collagen

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Collagen structure

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

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Fibrillar collagen

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

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Non fibrillar collagen

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

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Collagen synthesis

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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Defects in collagen synthesis

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

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Elastin

Elastic fibers in blood vessels, lungs, ligaments, and skin
Single protein with little post translational sorting

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Desmosomes

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

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Modified aa in elastin

Lysine to allysine

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Fibronectin

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

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Proteoglycans

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

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Difference between glycoproteins and proteoglycans

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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Major GAGs of ECM

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

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Synthesis of proteoglycans

Golgi

Disruption leads to mucopolysaccharidosis

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Degradation of proteoglycans

Lysosomes

Defects lead to mucopolysaccharidosis

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Role of proteoglycans

Structural support to tissues like cartilage and CT

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Aggrecan

Large accumulation of proteoglycans

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Significance of highly negatively charged proteoglycans

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

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Hyaluronic acid

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

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Chondroitin sulfate

Most common GAG
Major component of cartilage

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Dermatan sulfate

Highest charge density
Similar structure to chondroitin

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Heparan sulfate

Highest charged
Basement membranes
Anticoagulant

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Keratan sulfate

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

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Matrix metalloproteases

Proteins that digest other ECM proteins outside the cell

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Metal cofactor in MMPs

Zinc

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3 domains of an mmp

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

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How do you activate a zymogen MMp?

The propeptide domain with the cysteine switch must be removed

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

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

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Enamelysin

Degrades amelogenin
Amelogenesis imperfecta

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2 proteins involved in ECM signaling

Integrins, cytokines, growth factors

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Integrins

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

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Structure of Integrins

Dimer (alpha and beta subu) with divalent cations

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Cytokines

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

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Growth factors

Stimulate cell growth, proliferation and differentiation

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Functions of ECM

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