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Block 1 W5 > Extracellular Matrix Valenick > Flashcards

Extracellular Matrix Valenick Flashcards

1
Q

The communication b/n a cell and the ECM is mediated by what type of cell surface receptor?

A

Intergrins

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2
Q

when connections get disabled b/n the ECM and the cell, what can result?

A

congenital diseases such as DMD, Marfan syndrome etc.. Cancer and suseptibility to Infectious diseases

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3
Q

what type of receptor has bidirectional signaling, helps to modulate the ECM deposition & gene/protein expression and directly links the ECM to the intracellular cytoskeleton?

A

Integrins

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4
Q

integrins act as (blank), meaning they are activated by physical stress and stimulate a chemical response from the stress.

A

mechanotransducers

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5
Q

Integrins can stimulate 6 different pathways, what are they?

A

1) regulate gene expression
2) alter cytoskeleton organization
3) recruit additional integrins to cell membrane
4) promote cell growth
5) influence cell survival
6) promote ECM deposition

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6
Q

what is another term for promoting cell growth?

A

hypertrophy

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7
Q

what is mainly composed of proteins and carbohydrates, and forms and maintains the tissue architecture?

A

Extracellular Matrix (ECM)

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8
Q

what are two sub-types of ECMs?

A

interstitial (stromal) ECM & basal lamina ECM

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9
Q

Interstitial ECM is located where?

A

it surrounds cells and tissues and is abundant in connective tissue and it contains fibronectins

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10
Q

where is Basal lamina ECM found?

A

ECM is seen as the electron dense layer of the basal lamina (a component of the basement membrane).

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11
Q

what are the major components of the ECM?

A

Collagen, fibronectin, laminin, elastin, glycosaminoglycans, & proteoglycans.

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12
Q

what is the most abundant component of the ECM?

A

collagen- rope-like fibers that give tissue tensile strength.

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13
Q

what ECM component is mainly located in teh bones, tendons, skin, cartilage, arteries, lungs and liver?

A

Collagen

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14
Q

Collagen 1 and 2 form what type of triple helices?

A

left handed alpha-helix of 1000 AAs with a repetitive sequence of (Gly-X-Y)n
30% is glycine, 25% proline/hyroxyproline at X & Y

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15
Q

the assembly of 3 alpha chains into a right handed super helix is called what?

A

tropocollagen

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16
Q

how is procollagen formed?

A

Preprocollagen is synthesized in the ER where it forms a polyproline helix, the signal sequence is removed leaving procollagen

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17
Q

how is tropocollagen generated?

A

1) disulfide linkages occur between the alpha chains
2) various prolines and lysines are hyrdoxylated
3) collagen is O-glycosylated on hydroxylated lysines and N-glycosylated on asparagines
4) 3 alpha chains assemble into Rt handed helix
5) secreted from cell and ends are cleaved

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18
Q

what is responsible for the hyrdroxylation of lysines and prolines of collagen? and what do they require?

A

lysyl and prolyl hydroxylases that require Vitamin C

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19
Q

what type of integrin complex is affected in Muscular dystrophy?

A

dystoglycan complex integrins

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20
Q

Integrin receptors have very diverse specificity, including receptors for (blank)

A

collagen receptors, laminin receptors, leukocyte specific receptors, platelet receptors and RGD receptors.

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21
Q

in addition to the cytoskeleton, integrins can also link (blank).

A

the nucleus (lamin A)

22
Q

what is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane.

A

Costamere

23
Q

Independent of genotype, the ECM stiffness guides stem cell differentiation. What grew on the 3 ECM platforms (soft, firm, hard)

A

soft- nerve
firm- muscle
rigid- bone

24
Q

what is the pathway that links the micro-environment to the chromosomes?

A

ECM-Integrin-Cytoskeleton-Nucleus-DNA

25
Q

what is responsible for the covalent cross-linking found in tropocollagen?

A

lysyl oxidase- oxidative deamination of lysine and/or hydroxylysine - Cu2+ is required.

26
Q

cross-links are major determinant of what?

A

mechanical properties and strength of tissues

27
Q

what is a glycosylated multi-adhesive protein found in connective tissues and plasma?

A

Fibronectin

28
Q

there are two types of Fibronectin, what are they?

A

soluble form found in plasma
insoluble form found in the ECM
both encoded by 1 gene with alternative splicing

29
Q

what does Fibronectin interact with?

A

interacts with integrins via its RGD sequence and many other ECM components

30
Q

what are the roles of Fibronectin (Fn)?

A

1) development- essential for migration of cells along fibers
2) wound healing-links to fibrin clots to promote healing
3) cancer- cancer cells have Fn receptors that can bind ECM Fn at distant sites faciliating metastasis
4) cell proliferation and migration

31
Q

what is laminin (Ln)?

A

a multi-adhesive component enriched at the basal lamina where it binds cells to collagen 4
cross-shapes heterotrimer
has multiple isoforms
associated with cell differntiation

32
Q

what is laminin 2?

A

basement membrane protein that links integrin (or dystroglycan) to other ECM components

33
Q

what is lamin A

A

a nuclear envelope protein that forms filaments

34
Q

what is lamina?

A

the ECM component of basement membrane seen by electron microscopy

35
Q

what allows tissues to expand and contract?

A

Elastin

36
Q

where is Elastin most abundant?

A

blood vessels and lungs

37
Q

what has a highly cross-linked structure that is insoluble and rich in lysine, proline, valine, and glycine?

A

Elastin

38
Q

what does elastin use to initiate cross-linking?

A

lysyl oxidase

39
Q

what is the cross-link formed in elastin called?

A

desmosines

40
Q

dermatan, chondroitin, heparan, & heparin are the most common (blank).

A

glycosaminoglycans

41
Q

what are glycosaminoglycans (GAGs)?

A

unbranched polysaccharides of repeating disaccharide units built from amino sugars and uronic acids.

42
Q

what is the only true GAG?

A

hyaluronic acid

43
Q

Most GAGs are complexed to core proteins forming (blank).

A

proteoglycans

44
Q

what are the roles of GAGs and PGs?

A

provide flexible mechanical support?
act as sieves allowing the diffusion of small molecules and slowing the movement of proteins and movement of cells.
acts as a lubricant in joint and tissues subject to friction.
binds and sequestered soluble ECM proteins, thereby maintaining high concentration at the cell surface.

45
Q

what do Matrix Metalloproteinases do?

A

breakdown the ECM allowing the release of sequestered growth factors and allow for migration and tissue remodeling during development and response to injury.

46
Q

ECMs function in Cancer

A

ECM signals maintains dormant tumor cells, when the ECM is disrupted and reconstructed fibronectin and growth factors promote micrometastatic outgrowth.

47
Q

scurvy

A

abnormal collagen

48
Q

Marfan Syndrome

A

mutation in Fibrilin

49
Q

Mucopolysaccharidoses

A

mutation in proteoglycans

50
Q

Osterogenesis Imperfecta

A

mutation in collagen

51
Q

Supravalvular aortic stenosis

A

Elastin insufficiency

Block 1 W5 (11 decks)

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