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BMS Final > Structure And Function Of ECM > Flashcards

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
Q

Type VII collagen

A

Network forming

Anchoring fibrils @ epithelial-connective tissue junction

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26
Q

Type VII collagen mutation

A

Epidermal this

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27
Q

Transmembrane collagen

A

type XVII

Connects basement membrane to epithelium via anchoring filaments

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28
Q

Collagen biosynthesis

A

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
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29
Q

Fibril forming collagen is an __ event

A

Extracellularyl

After extension & cleavage..collagen molecules are termed tropocollagen…assembly then into micro fibril, then fibril, then fiber

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30
Q

Fibril associated collagens decorate outside of fibril type __ and is associated with type ___ collagen in cartilage

A

Fibril associated collagens code orate outside fibril type IX and is associated with type II collagen in cartilage

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31
Q

What collagen has reticular silver stain

A

Type III

Has more carbs, thinner fibrils, more branched, few bundles

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32
Q

Transmembrane XVII collagen is distributed in

A

Hemidesmosomes

–>bulbous pemphigoid

33
Q

Fibril associated collagen is type __

A

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
Q

Mutated type IX collagen?

A

Epiphyeal dysplasia…leads to arthritis

Important for joint integrity

35
Q

Type IV collagen is major component of __

A

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
Q

Type ____ collagen in anchoring fibrils; type _____ collagen is a transmembrane protein

A

VII, XVII

37
Q

What happen is type XVII transmembrane collagen-anchoring filaments mutated

A

-blistering btwn epithelium & basement membrane

38
Q

Can type I, II, III collagens all form fibrils?

A

Yes

39
Q

Do network forming collagens retain extension peptides during assembly

A

Yes

40
Q

Where does cleavage of pro peptides occur?

A

Outside cell

41
Q

Elastin is assembled ___

A

Extracellularyl as is collagen

42
Q

Elastic fibers are surrounded by

A

Micro fibrils composed of fibril lean

43
Q

Properties of elastin

A

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
Q

2 major molecular components in elastic fibers

A

Cross linked elastin monomers

Fibril in (participates in cross linking)

45
Q

Marfan syndrome mutation & presentation

A

Fibrilin 1 mutation

Results from miss ensue mutations in fibril in 1
Elongated extremities & enhanced rupture of aorta (lack of recoil during development)

46
Q

Hyperextended left skin due to mutation in what collagen

A

Type III

Susceptible to aneurism

47
Q

Epidermolysis bullosa due to what mutation

A

Type VII

Anchoring fibrils are disrupted…epithelium and basement membrane pealed away

48
Q

Elastomera results from….

A

Altered elastin

You pull skin and it stays out

49
Q

Glycosaminoglycans (GAG)

A

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
Q

Hyaluronic acid

A

GAG
Non sulfated
Not attached to protein

51
Q

Chondroitin sulfate

A

Sulfated

Attached to protein

52
Q

Heparan sulfate

A

Sulfated

Attached to protein

53
Q

Proteoglycans

A

Most GAG classes are covalently coupled to core protein

Hyaluronic acid exception!!!!!!

54
Q

Aggrecan

A

Prototypical proteoglycan found in cartilage

Aggrecan + type II, type IX all co exist in chondrocyte matrix

55
Q

Perlecan…type of gag chain and location

A

Heparin sulfate

In basal lamina

56
Q

Syndecan-1

A

Common Proteoglycan

Chondroitin sulfate and heparan sulfate…located in fibroblast & epithelial cell surface…cell adhesion!!!!!

57
Q

Aggrecan

A

Found in type II collagen cartilage; mechanical support..

58
Q

Perelman is localized where

A

Lamina densa of basement membrane ( EC)

59
Q

Proteoglycans can regulate what

A

Growth factor action

60
Q

What are the 2 heparan-sulfate Proteoglycans

A

Syndecan (membrane-associated); binds to cytoskeleton ..illustrates connection btwn ECM and internal signaling pathways

Perlecan (Extracellular)

61
Q

Fibronectin, laminin, nidogen (entactin) are

A

Matrix glycoproteins

62
Q

Fibronectin

A
  • 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
Q

Laminin

A
  • 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
Q

Integrins can bind to __ and __

A

Collagen and lamina

65
Q

Basal lamina components

A

Perlecan, laminin, nidogen, type IV collagen…..collagen can bind to everything including itself…so can laminin

66
Q

What do integrins do

A

Mediate communication btwn ECM and internal cell signaling

67
Q

Properties of integrins

A
  • diners
  • both subunits involved in binding substrate via RGD sequence
  • B subunit binds cytoskeleton (often actin). Can initiate formation of signaling complexes
68
Q

Integrins bind ___cytoskeleton and organize signaling molecules

A

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
Q

Mutation in B2 integrin

A

Leukocyte adhesion deficiency

Inability of WBC to b ind endothelium

70
Q

Mutation in B3 integrin

A

Glanzmann’s disease

Inability to bind fibrinogen during clotting

71
Q

Integrins and Syndecans are ____ proteins that both interact with ____

A

Cell membrane proteins, both interact with ECM components

72
Q

Hemidesmosomes contain ____

A

A6/B4 integrin

-anchors intermediate (keratin)

73
Q

A6/b1 integrin

A

Major receptor for laminin, may be altered in some forms of muscular dystrophy

74
Q

A5/b1 integrin

A

Links Fibronectin to actin filaments thru talin

75
Q

Activation of AIIB3 integrin can be caused by

A

Platelets

**b3 is found on platelets…binds fibrinogen during clotting

76
Q

Activation of B2 integrins can be caused by

A

Monocytes, neutrophils, lymphocytes

***b2 is found on WBCS…leukocyte adhesion deficiency prevents binding of white cells to endothelium

77
Q

T/F…integrin binding regulates IC signaling & other IC paths can also regulate integrin activity

A

Tru

78
Q

Lymphocyte binding to endothelium via selectin does what?

A

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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