Mtc Test 3: Cell Interactions, Ecm, Integrins

Front 1

Connective tissue

Back 1

ECM plentiful, cells sparse, mechanical load (most) borne by ECM

Front 2

Epithelial tissue

Back 2

cells tightly bonded in sheets, ECM sparse, most volume = cells; stresses borne by cell layer that rests on layer of ECM (basement membrane)

Front 3

Nerve cells

Back 3

surrounded by basement membranes

Front 4

Muscle

Back 4

skeletal muscle surrounded by basement membranes

Front 5

Glycocalyx

Back 5

carbohydrate-rich coating of exposed surfaces of cells
- prominent in intestinal epithelial cells (protective function)
- may be involved in mechanotransduction
- derived mainly from glycosyl moieties of PM glycoproteins and glycolipids

Front 6

Tight junctions

Back 6

- zonula occludens
- prevent diffusion of molecules through cell layers at interface between cells
- separate apical from basolateral surface of epithelial cells
- key proteins: occludin, members of claudin family

Front 7

Adherens junctions

Back 7

- zonula adherens
- continuous junction around epithelial cells
- provide strong adhesion between epithelial cells, attachment for actin microfilaments
- key transmembrane proteins: cadherins

Front 8

B-catenin

Back 8

binds cytoplasmic domain of cadherins
- binds alpha-catenin, which can also bind actin

Front 9

Desmosomes

Back 9

- macula adherens
- provide strong intracellular adhesions in localized spots
- intermediate filaments in these jxns: keratins/tonofilaments
- key transmembrane proteins: cadherins

Front 10

Pemphigus

Back 10

- disease that affects desmosomes
- individuals develop antibodies against desmosomal cadherins (desmogleins)
- leads to blistering of skin, major infections

Front 11

Hemidesmosomes

Back 11

- provide spot adhesions to basement membrane instead of to other cells, also attach intermediate filaments
- transmembrane proteins: integrins

Front 12

Pemphigoid

Back 12

individuals develop antibodies against hemidesmosomal proteins
- severe blistering, infection

Front 13

There is often loss of expression of what protein in invasive cancers?

Back 13

E-cadherin; decreased cell-cell adhesion

Front 14

Epithelial cell junctional complex =

Back 14

tight junction, adherens junction, desmosome

Front 15

What component of junctional complex also exist elsewhere?

Back 15

Desmosomes

Front 16

Focal adhesions

Back 16

- provide strong adhesion to ECM & attachment for actin microfilaments
- key transmembrane proteins: integrins

Front 17

Gap junctions allow passage of what type of compounds?

Back 17

Low molecular weight; < 1500 daltons

Front 18

Connexons

Back 18

- tube-like channels in gap junctions

Front 19

Connexin

Back 19

protein making up connexons (gap junctions)

Front 20

Gap junction permeability is regulated by:

Back 20

intracellular Ca++ and pH
- ex: if intracellular Ca rises, gap junctions close preventing cytoplasmic communication

Front 21

What does a gap junction look like on EM?

Back 21

tramline (on freeze fracture = big array of dots)

Front 22

Cadherins are dependent on....

Back 22

Calcium!!

Front 23

Are members of the Ig superfamily dependent on calcium?

Back 23

NOPE

Front 24

Which CAMs are primarily involved in cell-cell adhesion?

Back 24

Cadherins, Ig superfamily, Selectins

Front 25

Which CAM is often involved in cell-ECM adhesion?

Back 25

Integrin! Can be involved in cell-cell adhesion too tho

Front 26

What is the major adhesion molecule in adherens junctions?

Back 26

E-cadherin

Front 27

Cadherins

Back 27

- homophilic
- Ca-dependent
- link to actin cytoskeleton via catenins

Front 28

Integrins

Back 28

- heterophilic
- alpha-beta dimers
- divalent cation-dependent
- prominent receptors for ECM
- some mediate cell-cell interactions

Front 29

Integrins usually link to:

Back 29

actin cytoskeleton EXCEPT integrin in hemidesmosomes which link to keratin

Front 30

On surfaces of what cells do members of the Ig superfamily appear?

Back 30

neural, lymphoid, endothelial

Front 31

N-CAM

Back 31

member of Ig superfamily
- Ca++ independent
- homophilic

Front 32

Ig superfamily

Back 32

- do not require divalent cations
- involved in cell-cell adhesion
- homophilic or heterophilic

Front 33

Selectins are found on:

Back 33

leukocytes, endothelial cells

Front 34

Selectins mediate interactions between:

Back 34

blood cells and endothelial lining

Front 35

P-selectin

Back 35

stored in vesicles in platelets and endothelial cells
- in response to inflammatory signals, vesicles fuse with plasma membrane delivering P-selectin to endothelial cell surface

Front 36

Selectins bind what on interacting cell:

Back 36

carbohydrates

Front 37

Selectins

Back 37

-heterophilic
- calcium-dependent
- involved in leukocyte-endothelial cell interactions
- potential target for anti-inflammation therapies

Front 38

What are 5 functions of the extracellular matrix?

Back 38

- structural (strength of ligaments, etc)
- scaffold (basement membranes)
- barrier (basement membranes separate tissues)
- filter (kidney)
- regulatory (affects cell behavior)

Front 39

Collagens

Back 39

- assemble as triple helix
- fibrillar or non-fibrillar

Front 40

Fibrillar collagens

Back 40

found in connective tissues
- generate insoluble fibers of high tensile strength

Front 41

Non-fibrillar collagens

Back 41

found in basement membranes
- assemble to form networks

Front 42

Osteogenesis imperfecta

Back 42

mutations in type I collagen; weak bones

Front 43

Chondrodysplasias

Back 43

mutations in type II collagen found in cartilage
- bone and joint deformities

Front 44

Ehlers-Danlos Syndrome

Back 44

mutations in Type III collagen
- fragile skin and blood vessels
- hypermobile joints

Front 45

Scurvy

Back 45

proline hydroxylation for cross-linking requires vitamin C
- lack of vitamin C = scurvy; fragile blood vessels, loss of teeth

Front 46

Fibronectin

Back 46

- reverses transformed phenotype (transiently)
- increases cell adhesion to substratum
- secreted by many cells
- assembles into ECM on surface of cells

Front 47

What organ secretes soluble form of fibronectin that circulates in plasma?

Back 47

LIVER

Front 48

RGD sequence

Back 48

critical sequence of amino acids in primary cell binding domain

Front 49

Soluble RGD peptides

Back 49

potent inhibitors of cell adhesion to Fn and other ECM proteins (because they compete for binding)

Front 50

Integrilin

Back 50

synthetic peptide based on RGD sequence being used to inhibit thrombosis formation (esp in situations like angioplasty)

Front 51

Fibronectin is often concentrated in:

Back 51

Focal adhesions

Front 52

What happens to fibronectin when cells become cancerous?

Back 52

Fibronectin lost on cell surface; giving transformed cells extra Fn will often restore adhesion and return them to more normal morphology

Front 53

Elastin

Back 53

major protein that forms elastic fibers
- most abundant proteins in arteries

Front 54

Marfans Syndrome

Back 54

results from mutations in fibrillin, another protein in elastic fibers

Front 55

Basement membranes are composed of:

Back 55

laminin, non-fibrillar collagens, proteoglycans

Front 56

Laminin

Back 56

major constituent of basement membrane
- 3 polypeptide chains arranged in cross-like config
- contains binding sites for other ECM components

Front 57

What are GAGs good for?

Back 57

-occupy space
- resist compression
- lubricants

Front 58

What are proteoglycans good for?

Back 58

Bind other ECM components and growth factors

Front 59

Do all integrins bind through RGD sequence?

Back 59

Nope!

Front 60

Beta 1, 2 and 3 integrins all link to:

Back 60

Actin filaments

Front 61

B4 integrins are different bc they:

Back 61

have long cytoplasmic domains and link to intermediate filaments in hemidesmosomes

Front 62

B2 integrins only found on:

Back 62

leukocytes

Front 63

B2 integrins bind to:

Back 63

cell adhesion molecules on endothelial cells and involved in recruitment of leukocytes from circulation

Front 64

B3 integrins pairs with:

Back 64

either of 2 alpha chains, alphavB3 or alphaIIbB3

Front 65

AlphaIIbB3 integrin:

Back 65

only found on platelets; normally inactive but becomes competent to bind fibrin/fibrinogen when platelets activated; target for integrillin

Front 66

Glanzmann's Thrombasthenia

Back 66

alphaIibB3 missing or mutated
- these ppl can't form effective blood clots

Front 67

FAK

Back 67

focal adhesion kinase
- becomes activated when integrins bind ECM components
- phosphorylations affect growth and differentiation of cells
- increased activity or expression in many invasive tumor cells

Front 68

LAD (Leukocyte Adhesion Deficiency)

Back 68

leukocytes don't express B2 integrins; fail to adhere to endothelial cells
- failure to mount inflammatory response or combat bacterial infections

Front 69

What are the steps of leukocyte recruitment?

Back 69

1. Rolling adhesion
2. Firm adhesion
3. Transmigration

Front 70

What proteins involved in initial adhesion of leukocytes?

Back 70

Selectins

Front 71

What proteins involved in strong adhesion of leukocytes?

Back 71

ICAM-1

Front 72

B2 integrins become activated for which specific cells?

Back 72

Neutrophils, monocytes

Front 73

What integrin becomes activated for T cells?

Back 73

alpha4B1

Front 74

T cells bind to what protein on endothelial surface?

Back 74

VCAM

Front 75

Some MS treatments bind what integrins:

Back 75

alpha 4 integrins on surface of T lymphocytes

Front 76

What is a potential therapy for heart attacks?

Back 76

blocking interactions between B2 integrins and ICAM-1