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Exam 2 > Cell Adhesion > Flashcards

Cell Adhesion Flashcards

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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
Naxos Disease
mutation in C-terminal of plakoglobins wooly hair, heart problems, crusty hands, early death plagoglobin fails to localize at intercellular junctions
26
Carvajal Syndrome
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
arhythmogenic cardiomyopathy
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
staphylococcal scalded skin bullous impetigo
Dsg1 - bacterial toxins attack
29
ectodermal dysplasia
plakophilin genetic
30
size of filaments
actin - 5 nm intermediate - 10 nm (highly stable!) microtubules - 25 nm
31
Intermediate filaments
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
Intermediate filament rod
central rod - 310 AA 4 highly conserved alpha helical domains 3 not conserved non-alpha helical domains head and tail: varying, non helical
33
intermediate filament dimer
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
Intermediate filament structure
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
mutations in intermediate filaments
mutations at conserved ends of rods - cause keratin clumping! mutations in L1-2 - affect packing! weaker!
36
Structure of Skin
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
EBS
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
K5/K14
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
Dowling-Meara
most severe EBS filaments clump! no long filaments mutations at the ENDS of rods
40
Weber Cockayne EBS
Mutations at central non helical (L1-2 Region) - and at very beginning of rod, mild - thin!
41
Koebner EBS
most mold - mutations in helical/intron regions? thin filaments
42
K1/K10
keratin in epidermal suprabasal layer, first express K5/K14 then change to K1/K10 mutations --\> EH
43
EH
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
JEB
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
hemidesmosomes
keratin - K5/K14 intracellular plaque - Plectin, BPAG1 transmembrane proteins (integrin a5b4, BPAG2) anchoring filaments - Laminin V Lamina densa - Collagen IV, Laminin
46
JEB + muscular dystrophy
mutation in plectin
47
GABEB
BPAG-2 mutation (transmembrane protein) rare
48
JEB + pyloric atresia
a6b4 integrin - projectile vomiting
49
Classical JEB
laminin V - anchoring filaments mutation
50
DEB
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
Collagen VII
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
immunoflourescence against Collagen IV in basement membrane. Where are blisters for DEB and EBS?
membrane on roof/floor of BLISTER DEB - collagen IV on blister roof EBS - collagen IV on blister floor
53
antibody panel for BPAG1/2. where is it on blister?
EBS - base JEB - roof DEB - roof
54
antibody panel for Laminin 1. Where on blister?
EBS - base JEB - base DEB - roof
55
antibody for Collagen IV. where on blister?
EBS - base JEB - base DBS - roof
56
Bullous Pemphigoid
autoabs bound to bpag 1, blisters between epidermis and dermis
57
Cicatricial Pemphigoid
autoantibodies to Laminin V blisters between empidermis and dermis eye
58
Disorders of Spinous layer
GENETIC: EPPK (K9) EH (K1/K10) AUTOIMMUNE: Pemphigus foliaceus (DSG1)
59
Disorders of basal layer
GENETIC: EBS - K5/K14 AUTOIMMUNE: Pemphigus vulgaris (Dsg 3)
60
Disorders of Basal Layer/Lamina interface
GENETIC: JEB: a6B4, BPA2 AUTOIMMUNE: Bullous Pemphigoid (BPAG2, BPAG1)
61
Disorders of Dermis
GENETIC: DEB (Coll VII) AUTOIMMUNE: EB Acquisita (Col VII)
62
hemidesmosomes/EB structure

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