Extracellular Matrix Valenick

Question 1

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

Answer 1

Intergrins

Question 2

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

Answer 2

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

Question 3

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?

Answer 3

Integrins

Question 4

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

Answer 4

mechanotransducers

Question 5

Integrins can stimulate 6 different pathways, what are they?

Answer 5

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

Question 6

what is another term for promoting cell growth?

Answer 6

hypertrophy

Question 7

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

Answer 7

Extracellular Matrix (ECM)

Question 8

what are two sub-types of ECMs?

Answer 8

interstitial (stromal) ECM & basal lamina ECM

Question 9

Interstitial ECM is located where?

Answer 9

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

Question 10

where is Basal lamina ECM found?

Answer 10

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

Question 11

what are the major components of the ECM?

Answer 11

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

Question 12

what is the most abundant component of the ECM?

Answer 12

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

Question 13

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

Answer 13

Collagen

Question 14

Collagen 1 and 2 form what type of triple helices?

Answer 14

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

Question 15

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

Answer 15

tropocollagen

Question 16

how is procollagen formed?

Answer 16

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

Question 17

how is tropocollagen generated?

Answer 17

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

Question 18

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

Answer 18

lysyl and prolyl hydroxylases that require Vitamin C

Question 19

what type of integrin complex is affected in Muscular dystrophy?

Answer 19

dystoglycan complex integrins

Question 20

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

Answer 20

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

Question 21

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

Answer 21

the nucleus (lamin A)

Question 22

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

Answer 22

Costamere

Question 23

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

Answer 23

soft- nerve
firm- muscle
rigid- bone

Question 24

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

Answer 24

ECM-Integrin-Cytoskeleton-Nucleus-DNA

Question 25

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

Answer 25

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

Question 26

cross-links are major determinant of what?

Answer 26

mechanical properties and strength of tissues

Question 27

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

Answer 27

Fibronectin

Question 28

there are two types of Fibronectin, what are they?

Answer 28

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

Question 29

what does Fibronectin interact with?

Answer 29

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

Question 30

what are the roles of Fibronectin (Fn)?

Answer 30

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

Question 31

what is laminin (Ln)?

Answer 31

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

Question 32

what is laminin 2?

Answer 32

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

Question 33

what is lamin A

Answer 33

a nuclear envelope protein that forms filaments

Question 34

what is lamina?

Answer 34

the ECM component of basement membrane seen by electron microscopy

Question 35

what allows tissues to expand and contract?

Answer 35

Elastin

Question 36

where is Elastin most abundant?

Answer 36

blood vessels and lungs

Question 37

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

Answer 37

Elastin

Question 38

what does elastin use to initiate cross-linking?

Answer 38

lysyl oxidase

Question 39

what is the cross-link formed in elastin called?

Answer 39

desmosines

Question 40

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

Answer 40

glycosaminoglycans

Question 41

what are glycosaminoglycans (GAGs)?

Answer 41

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

Question 42

what is the only true GAG?

Answer 42

hyaluronic acid

Question 43

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

Answer 43

proteoglycans

Question 44

what are the roles of GAGs and PGs?

Answer 44

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.

Question 45

what do Matrix Metalloproteinases do?

Answer 45

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

Question 46

ECMs function in Cancer

Answer 46

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

Question 47

scurvy

Answer 47

abnormal collagen

Question 48

Marfan Syndrome

Answer 48

mutation in Fibrilin

Question 49

Mucopolysaccharidoses

Answer 49

mutation in proteoglycans

Question 50

Osterogenesis Imperfecta

Answer 50

mutation in collagen

Question 51

Supravalvular aortic stenosis

Answer 51

Elastin insufficiency