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Structure And Function Of ECM Flashcards

1
Q

3 layers of basement membrane

A

Lamina Rara
Lamina densa
Lamina reticularis

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2
Q

Lamina Lucida/lamina/Rara

A

Some fibroid toon & specific lamin 5

Type XVII collagen from cell membrane

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3
Q

Lamina densa

A

Laminin 1, type IV collagen, Perelman, nitrogen

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4
Q

Lamina reticularis

A

Types 1, III, VII collagen
Proteoglycans
Fibronectin

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5
Q

Stroma

A

Major component of adult ECM
Located outside lamina reticularis of BM

Secreted by fibroblasts & specialized mesenchymal cells

In adult, different tissues have diff stroma like matin organization (ex: tendon, a lot..liver..little)

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6
Q

What’s in the stroma

A

Fibronectin, collagen I, III, VII, elastic fibers

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7
Q

How does matrix interacts with cell surface receptors

A

Integrin & syndecan

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8
Q

Integrin

A

Cell type specific integral membrane proteins that serve as receptors

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9
Q

Syndecans

A

Specific heparin sulfate containing proteoglycans that span cell membrane & interact with actin filaments

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10
Q

Basal lamina contains

A

Lamin in, Fibronectin, type IV collagen, heparin sulfate proteoglycans, entactin

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11
Q

Stroma consists of ____ cells, ___ matrix ____ connective tissue

A

Few cells, lots of matrix, dense irregular connective tissue

In some tissues, specialized fibroblasts secrete stroma

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12
Q

Structure of collagen

A
  • triple stranded helical molecule; 3 monomer alpha chains wrapped around each other
  • glycine every 3rd amino acid..small side chain fits inside
  • proline, lysine, and hydroxylases forms present and contribute to helix stability (hydrogen binding)…can be delaminates to produce fibril (triple helical structures assemble into fibrils)
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13
Q

Collagen fiber is assembled where

A

Extracellularyl

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14
Q

Fibril forming collagens (fibrillar) (generally found in stroma)

A

I, II, III, V

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15
Q

Type I collagen

A

Fibrillar forming
Most abundant (90%)
Tendon, bone, lung, skin, internal organs
Polymerized form: fibril

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16
Q

Mutation in type I collagen

A

Osteogenesis imperfect a bullosa

Brittle bones

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17
Q

Type II collagen

A

Fibrillar
Polymerized: fibril
Cartilage (50% cartilage)

I vertebral disc, notochord, vitreous humor

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18
Q

Mutation in type II collagen

A

Chondrodysplasia

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19
Q

Type III collagen

A

Fibrillar

Skin, aorta (reticular collagen); stained with silver (more carbs, smaller fibrils), blood vessels, internal organs

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20
Q

Mutation in type III collagen

A

Euler-Danlos syndrome (hyperextended skin)

Susceptibility to aneurism

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21
Q

Fibril-associated collagens with interrupted triple helix

A

Type IX, XII

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22
Q

Type IX collagen

A

Fibril associated
Polymerized form: later all association with type II fibrils

Cartilage (decorated outside type II collagen fibrils)

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23
Q

Non fibrillar (“network forming”) collagens

A

Type IV, VII

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24
Q

Type IV collagen

A

Sheet like network

Basal lamina/lamina densa/basement membrane

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25
Type VII collagen
Network forming Anchoring fibrils @ epithelial-connective tissue junction
26
Type VII collagen mutation
Epidermal this
27
Transmembrane collagen
type XVII Connects basement membrane to epithelium via anchoring filaments
28
Collagen biosynthesis
Alpha chains synthesized as pro-alpha chains on RER-attached polysomes - hydroxylation of selected pro lines & lysines (need VitC) - glyocsylation of selected hydrolysines - self assembly of 3 pro-alpha chains & procollagen triple helix formation - secreted from ER/Golgi - outside cell..procollagen..cleavage of peptides & self assembly into fibril - -SINGLE GLY MUTATION IN PRIMARY STRUCTURE CAN ALTER HELIX..MANY ENZYMATIC STEPS WITH POSSBILITY FOR ERROR
29
Fibril forming collagen is an __ event
Extracellularyl After extension & cleavage..collagen molecules are termed tropocollagen...assembly then into micro fibril, then fibril, then fiber
30
Fibril associated collagens decorate outside of fibril type __ and is associated with type ___ collagen in cartilage
Fibril associated collagens code orate outside fibril type IX and is associated with type II collagen in cartilage
31
What collagen has reticular silver stain
Type III Has more carbs, thinner fibrils, more branched, few bundles
32
Transmembrane XVII collagen is distributed in
Hemidesmosomes -->bulbous pemphigoid
33
Fibril associated collagen is type __
Type IX - some interruption of triple helix thus less rigid; form hinge - decorated outside of type II collagen of chondrocytes - important for joint integrit
34
Mutated type IX collagen?
Epiphyeal dysplasia...leads to arthritis Important for joint integrity
35
Type IV collagen is major component of __
Lamina densa (basal lamina) - chicken wire array - multiple interruptions of helix; extension peptides not cleaved..both termini interact...little Extracellularyl processing of procollagen chains!!!
36
Type ____ collagen in anchoring fibrils; type _____ collagen is a transmembrane protein
VII, XVII
37
What happen is type XVII transmembrane collagen-anchoring filaments mutated
-blistering btwn epithelium & basement membrane
38
Can type I, II, III collagens all form fibrils?
Yes
39
Do network forming collagens retain extension peptides during assembly
Yes
40
Where does cleavage of pro peptides occur?
Outside cell
41
Elastin is assembled ___
Extracellularyl as is collagen
42
Elastic fibers are surrounded by
Micro fibrils composed of fibril lean
43
Properties of elastin
Highly cross linked via unique amino acids and provide resilience Allow stretching and recoil of connective tissue Aorta: a lot of high elastic fiber
44
2 major molecular components in elastic fibers
Cross linked elastin monomers Fibril in (participates in cross linking)
45
Marfan syndrome mutation & presentation
Fibrilin 1 mutation Results from miss ensue mutations in fibril in 1 Elongated extremities & enhanced rupture of aorta (lack of recoil during development)
46
Hyperextended left skin due to mutation in what collagen
Type III Susceptible to aneurism
47
Epidermolysis bullosa due to what mutation
Type VII Anchoring fibrils are disrupted...epithelium and basement membrane pealed away
48
Elastomera results from....
Altered elastin | You pull skin and it stays out
49
Glycosaminoglycans (GAG)
Long unbranded polysaccharide chains - repeating disacharides - alternating acid sugar and amino charged; very negatively charged, highly extended, osmotic ally active (bind water) - resist compression (joints, vitreous; synovial fluids loaded with gags)
50
Hyaluronic acid
GAG Non sulfated Not attached to protein
51
Chondroitin sulfate
Sulfated | Attached to protein
52
Heparan sulfate
Sulfated | Attached to protein
53
Proteoglycans
Most GAG classes are covalently coupled to core protein | Hyaluronic acid exception!!!!!!
54
Aggrecan
Prototypical proteoglycan found in cartilage Aggrecan + type II, type IX all co exist in chondrocyte matrix
55
Perlecan...type of gag chain and location
Heparin sulfate In basal lamina
56
Syndecan-1
Common Proteoglycan Chondroitin sulfate and heparan sulfate...located in fibroblast & epithelial cell surface...cell adhesion!!!!!
57
Aggrecan
Found in type II collagen cartilage; mechanical support..
58
Perelman is localized where
Lamina densa of basement membrane ( EC)
59
Proteoglycans can regulate what
Growth factor action
60
What are the 2 heparan-sulfate Proteoglycans
Syndecan (membrane-associated); binds to cytoskeleton ..illustrates connection btwn ECM and internal signaling pathways Perlecan (Extracellular)
61
Fibronectin, laminin, nidogen (entactin) are
Matrix glycoproteins
62
Fibronectin
- exists as dimer (healed together by disulfide bonds) in wound healing - plasma Fibronectin, cellular Fibronectin - 2 binding sites for integrins, collagen, heparin, fibrin - modular organization--binding mediated thru RGD sequence - multiple domains in modular array can interoconnect series of cell-matrix components at surface and in matrix
63
Laminin
- major component of basal lamina - 3 disulfide linked polypeptide chains - binding sites for cell surface receptors (integrins, type IV collagen, adhesion proteins (nidogen) - adhesion... - binding to major integrin occurs thru RGD
64
Integrins can bind to __ and __
Collagen and lamina
65
Basal lamina components
Perlecan, laminin, nidogen, type IV collagen.....collagen can bind to everything including itself...so can laminin
66
What do integrins do
Mediate communication btwn ECM and internal cell signaling
67
Properties of integrins
- diners - both subunits involved in binding substrate via RGD sequence - B subunit binds cytoskeleton (often actin). Can initiate formation of signaling complexes
68
Integrins bind ___cytoskeleton and organize signaling molecules
Actin - integrins cluster after binding substrate..organize cytoskeleton (bind actin binding proteins & fially actin) - focal adhesions form @ site of bound integrin...recruit signaling molecules (focal adhesion kinase, then others)
69
Mutation in B2 integrin
Leukocyte adhesion deficiency Inability of WBC to b ind endothelium
70
Mutation in B3 integrin
Glanzmann's disease Inability to bind fibrinogen during clotting
71
Integrins and Syndecans are ____ proteins that both interact with ____
Cell membrane proteins, both interact with ECM components
72
Hemidesmosomes contain ____
A6/B4 integrin -anchors intermediate (keratin)
73
A6/b1 integrin
Major receptor for laminin, may be altered in some forms of muscular dystrophy
74
A5/b1 integrin
Links Fibronectin to actin filaments thru talin
75
Activation of AIIB3 integrin can be caused by
Platelets ****b3 is found on platelets...binds fibrinogen during clotting
76
Activation of B2 integrins can be caused by
Monocytes, neutrophils, lymphocytes ***b2 is found on WBCS...leukocyte adhesion deficiency prevents binding of white cells to endothelium
77
T/F...integrin binding regulates IC signaling & other IC paths can also regulate integrin activity
Tru
78
Lymphocyte binding to endothelium via selectin does what?
Changes B2 integrin conformation...allows its binding to endothelial surface receptors Inital leukocyte interaction with endothelium is via low affinity receptor (Selectin)...IC signaling alters integrin conformation...allows specific high affinity binding to endothelium & ultimately leukocyte infiltration form blood to tissue *for clots, makes sure clots only when needed **integrin on WBS..selectin on endothelium

BMS Final (3 decks)

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