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Exam 2 > Cell Adhesion > Flashcards

Cell Adhesion Flashcards

1
Q

Ig-CAMs

A

first, to rec self, Igs developed from Ig-CAMS to recognize other transient and dynamic neural and lymphocyte interactions - mediates specific interactions between lymphocytes and neural homophilic (N-cam + N-cam) and heterophilic (N-Cam binds to integrin, binds to ECM) Calcium independent Subverted as viral receptors - viruses can bind and enter cells - unregulated after virally induced damage! increase effect

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2
Q

proteoglycans

A

bind cells to ECM calcium independent glycerin side chains - bind growth factors, sequester and weather cell adhesion + signal, linker proteins, like cartilage, CD44 - expressed in cancer cells

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3
Q

Selectins

A

Calcium dependent! for strcture bind to sugars via a lectin domain sugars - encode greater repertoire of specificity than proteins lymphocytes patrolling endothelial lining of blood vessels - rec special sugars on the endothelial proteins (vascular addressins), used to roll along (need integrings for extravasation) weak adhesion and rolling!

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4
Q

Integrins

A

heterodimer - alpha and beta subunits! bind divalet cations (ca2+) and induce conf change in adhesive interface - adhesion bind to many ECM proteins of basal lamina (collagen, fibronectin, laminin) conformational change –> activate ectodomain –> cluster ingegrins in adhesive patches (hemidesmosomes, focal contacts) at these sites –> bind cytoskeleton through adaptor proteins bound to cytoplasmic domain

connect ECM to the cytoskeleton at focal contacts and hemidesmosomes

potentiate growth and survival signals! GF –> stim cell to proliferate –> with augment pway only if integrins are engaged (cells have to be in contact w the matrix for cell survival)

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5
Q

Cadherins

A

bind Ca 2+ and mediate cell-cell adhesion

at desmosomes and adherens junctions

highly conserved! 5 extracellular repeats of 110 AA - each ectodoman has negatively charged AA - bind Ca2+ ions –> conf change –> rigidifies –> adhesion/protect from proteolysis

each ectodomain folds into beta barrel (like Ig-CAMs)

homophilic and specific

loss associated w cancer

initiate cell contact w cadherins on tips of filopodia

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6
Q

puncta adherens

A

caderens used to initiate cell contact

on filopodial tips

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7
Q

zonula adherens

A

cardiac discs, belts in polarized epithelia

in polarized cell - arrange in belt, just below apical surface, harness actin filaments ot plasma membrane

initiate cell adhesion and transducing changes in cell and tissue shape!

initate cell adhesion

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8
Q

catenins

A

promote clustering of cell-cell adherins junctions

velcro! like zipper

alpha - bound to actin

beta - bound do E-cadherin

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9
Q

structure of adherens junction

A

velcro - caderens not sticky by themselves!

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10
Q

p120

A

part of adherens junction

prevents cadherin endocytosis and regulates actin remodeling

not statically on cell surface

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11
Q

plankglobin/beta-catenin

A

links between cadherins and alpha catenin

binds to cadherins via positively charged groove - bridge between alpha catenin and E-cadherin - if phosphorylated, ca’t bind! can regulate adhesion post-translationally

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12
Q

alpha-catenin

A

regulate local actin assembly and organization at sites of cell-cell adhesion

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13
Q

teminal bar complex

A
  1. tight junction
  2. zonula adherens
  3. desmosome

zonula adherens and desmosome - widened intracellular space with filament

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14
Q

E-cadherin

A

associated with stable differentiated epithelial tissue- if lose it, invasive, migratory, rapid proliferation

N-cadherin gain associated with tumor metastisis and invasion

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15
Q

adherens and cancer

A

E-cadherin loss

N-cadherin gain

alpha catenin loss

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16
Q

Wnt signaling

A

Wnt - function of catenins outside of cell junctions, wnt –> allows beta catenin to accumulate outside of cell adhesion

if no wnt –> beta catenin would not be outside of cell adhesion because it would be drgraded by APC

Wnt - inactivates cytoplasmic complex of APC that targets cytosolic beta-catenin for degredation - no beta catenin degredation!

beta-catenin can enter nucleus and regulate growth genes

colon cancer = mutation in APC (APC destroys beta-catenin if not in the cell junction)

APC facilitates beta-catenin degredation - increase in beta-catenin in colon cancer –> not degraded –> activates genes!

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17
Q

Desmosomes

A

symmetrical circular membrane specializations

REINFORCE cell adhesin

bind intermediate filaments (keratin) - form resilient supracellular web, 10 nm intermediate filaments

found in all epithelia but most in stressed epithelia and heart (intercalated discs)

wider, dense, parallel plaques - 20-30 nm

midlines

buttons and suspenders

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18
Q

Desmosome structure

A
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19
Q

plakoglobin

plakophilin

A

desmosomal catenins

desmosomal cadherens bind directly

intermediate filament cytoskeleton linkers

highly conserved and identical in all tissues

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20
Q

desmoglians

desmocollins

A

cadherins in desmosomes

ectodomains are similar but cytoplasmic domains are different

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21
Q

Pepmhigus vulgaris

A

autoimmune

desmoglian 3

cadherin affected by pemphigus vulgaris - antibodies attack dsg3 - skin and oral cavity

deep blisters above basal cells and mucus membrane

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22
Q

pemphigus foliaceus

A

dsg1

autoimmune

desmoglian, cadherin attacked

target of pemphigus foliaceus autoantibodies, Staph A. and Bollous Impetigo toxins

superficial blisers

toxins cleave Dsg1 - crustier higher level

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23
Q

desmoplakin

A

connect to intermediate filaments! like alpha-catenin?

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24
Q

Difference between desmosomes and adherens junctions

A
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25
Q

Naxos Disease

A

mutation in C-terminal of plakoglobins

wooly hair, heart problems, crusty hands, early death

plagoglobin fails to localize at intercellular junctions

26
Q

Carvajal Syndrome

A

autosomal recessive mutation in desmoplakin (C-terminal truncation)

connects desmosomes to intermediate filaments

haploinsufficiency

heart defects

no desmoplakin or plakoglobin linked to intercalated discs

27
Q

arhythmogenic cardiomyopathy

A

mutations in genes encoding desmosomal proteins

desmocollins, desmoglein, desmoplakin, plakoglobin, plakophillin

cells don’t beat together - need cell adhesion sites

not protected from sheer stress by mechanical junctions (adherens junctions and desmsomes) at intercalated discs

28
Q

staphylococcal scalded skin

bullous impetigo

A

Dsg1 - bacterial toxins attack

29
Q

ectodermal dysplasia

A

plakophilin

genetic

30
Q

size of filaments

A

actin - 5 nm

intermediate - 10 nm (highly stable!)

microtubules - 25 nm

31
Q

Intermediate filaments

A

major proteins (10-85% of total proteins)

mechancal integrators that resist stress and provide structural integrity

large family

differentially expressed to serve specific cytoarchitectural needs

specific needs per cell

supracellular web - in tissue, through connections to desmisomes/hemidesmosomes

32
Q

Intermediate filament rod

A

central rod - 310 AA

4 highly conserved alpha helical domains

3 not conserved non-alpha helical domains

head and tail: varying, non helical

33
Q

intermediate filament dimer

A

first and fourth residues are hydrophobic! these residues align when 2 rods coil together to make a greasy seal

parallel - heads together, tails together

1 acidic, 1 basic (some homopolymeric)

2 dimers associate antiparallel and staggered

34
Q

Intermediate filament structure

A

dimers - antiparallel to make tetramers

tetramers elongate linearly to make protofilaments

two protofilaments stact to form protofibril

4 protofibrils twine around each other to for filament

32 polypeptides!

35
Q

mutations in intermediate filaments

A

mutations at conserved ends of rods - cause keratin clumping!

mutations in L1-2 - affect packing! weaker!

36
Q

Structure of Skin

A

EPIDERMIS: prevent water loss and infection

Stratum Corneum (dead)

Granular layer

Spinus layers - terminally differentiated in skin, make keratins, ross link, make h2o resistent barrier, die

basal layer - tall cells - high nucleus to cytoplasm ration - proliferation

basal lamina

DERMIS

37
Q

EBS

A

epidermal blistering just above basal lamina

aggravated by trauma and heat

3 subtypes: Dowling Meara, Weber Cockayne, Koebner

absence or weakening of filament network

keratin aggregates

intraepidermal cytolysis

within basal epidermal cells - gap in tall mitotically active cells - lack of filament in that layer OR lots of keratin (severe), weak filaments (mild)

38
Q

K5/K14

A

genes for keratins in basal cells of all stratified epithelia

Keratins - obligate heterodimers of one acidic and one basic keratin polypeptide

Dominant: abnormal protein produced which disrupts large molecular complex, if mutation in K5-K14 still needs it

Recessive: insufficient functional protein produced

39
Q

Dowling-Meara

A

most severe EBS

filaments clump! no long filaments

mutations at the ENDS of rods

40
Q

Weber Cockayne EBS

A

Mutations at central non helical (L1-2 Region) - and at very beginning of rod, mild - thin!

41
Q

Koebner EBS

A

most mold - mutations in helical/intron regions? thin filaments

42
Q

K1/K10

A

keratin in epidermal suprabasal layer, first express K5/K14 then change to K1/K10

mutations –> EH

43
Q

EH

A

flacid blisters, thick keratotic plaques

AD - mutations in genes encoding K1/K10 keratins in suprabasal epidermal cells

same hotspots at the end of the rods on K1/K10

mosaic EH - post zygotal mutation

mutation is higher - still have mitotically active layer, proliferation to overcompensate

44
Q

JEB

A

hemidesmosomes! blister at basal lamina region

hemidesmosomal adhesion to basal lamina

present at birth, some mortality

large blisters between epidermis and dermis

autosomal receessive - many different types due to proteins involved in cell-matrix adhesion

failure to thrive and iron deficiency

45
Q

hemidesmosomes

A

keratin - K5/K14

intracellular plaque - Plectin, BPAG1

transmembrane proteins (integrin a5b4, BPAG2)

anchoring filaments - Laminin V

Lamina densa - Collagen IV, Laminin

46
Q

JEB + muscular dystrophy

A

mutation in plectin

47
Q

GABEB

A

BPAG-2 mutation (transmembrane protein)

rare

48
Q

JEB + pyloric atresia

A

a6b4 integrin - projectile vomiting

49
Q

Classical JEB

A

laminin V - anchoring filaments mutation

50
Q

DEB

A

in dermis! mutationin Collagen VII anchoring fibrils

no anchoring fibrils

lots of scarring

AR and AD - all due to Collagen VII mutations - the major component of anchoring fibrils

increased risk for squamous cell carcinoa

infection

51
Q

Collagen VII

A

forms anchoring fibrils, stich dermis to epidermis by binding to laminins and collagen IV in basal lamina and anchoring plaques

collagedns are connected to lamins - triple helix and non collagenous head and tail

2 tails line up and cleaved off - bundle - 6 polypeptides - 3 heads on one side, 3 on the other

52
Q

immunoflourescence against Collagen IV in basement membrane. Where are blisters for DEB and EBS?

A

membrane on roof/floor of BLISTER

DEB - collagen IV on blister roof

EBS - collagen IV on blister floor

53
Q

antibody panel for BPAG1/2. where is it on blister?

A

EBS - base

JEB - roof

DEB - roof

54
Q

antibody panel for Laminin 1. Where on blister?

A

EBS - base

JEB - base

DEB - roof

55
Q

antibody for Collagen IV. where on blister?

A

EBS - base

JEB - base

DBS - roof

56
Q

Bullous Pemphigoid

A

autoabs bound to bpag 1, blisters between epidermis and dermis

57
Q

Cicatricial Pemphigoid

A

autoantibodies to Laminin V

blisters between empidermis and dermis

eye

58
Q

Disorders of Spinous layer

A

GENETIC:

EPPK (K9)

EH (K1/K10)

AUTOIMMUNE:

Pemphigus foliaceus (DSG1)

59
Q

Disorders of basal layer

A

GENETIC:
EBS - K5/K14

AUTOIMMUNE:

Pemphigus vulgaris (Dsg 3)

60
Q

Disorders of Basal Layer/Lamina interface

A

GENETIC:

JEB: a6B4, BPA2

AUTOIMMUNE:

Bullous Pemphigoid (BPAG2, BPAG1)

61
Q

Disorders of Dermis

A

GENETIC:

DEB (Coll VII)

AUTOIMMUNE:

EB Acquisita (Col VII)

62
Q

hemidesmosomes/EB structure

A

Exam 2 (8 decks)

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