15 - Epidermal and Dermal Adhesion Flashcards
1
Q
Major cellular structures involved at cell-cell junctions in the epidermis
A
Desmosomes
2
Q
Basement membrane adhesion complexes and related structures at the dermal-epidermal junction
A
Hemidesmosomes
3
Q
Desmosome is also known as
A
Macula adherens
4
Q
Major cell adhesion junction of the epidermis
A
Desmosomes
5
Q
Anchor apposing keratinocyte cell surface membranes to the intercellular keratin intermediate filament network
A
Desmosome
6
Q
Desmosomal cadherins
A
Desmogleins
Desmocollins
7
Q
Plakins
A
Desmoplakin
Envoplakin
Periplakin
8
Q
Armadillo family proteins
A
Plakoglobin
Plakophilins
9
Q
Transmembrane proteins whose extracellular amino-terminal domains interact to form the trans-adhesive interface between cells, represented by the electron-dense midline of the desmoglea
A
Desmosomal cadherins
10
Q
Contains the desmosomal cadherin cytoplasmic tails, with plakoglobin and the desmoplakin amino-terminal domain, and plakophilin
A
Outer dense plaque
11
Q
Desmoplakin carboxyl-terminus interacts with keratin intermediate filaments, producing the
A
Inner dense plaque
12
Q
Desmosomal cadherins mediate _____-dependent adhesion in a variety of epithelial tissues
A
Calcium
13
Q
In humans, there are _____ desmoglein isoforms and _____ desmocollin isoforms
A
4
3
14
Q
Expressed predominantly in the differentiated cells of the superficial epidermis
A
Dsg1
Dsg4
Dsc1
15
Q
Expressed more strongly in the basal and/or suprabasal layers
A
Dsg2
Dsg3
Dsc2
Dsc3
16
Q
Dsg: Largely limited to statified squamous epithelia in the skin
A
Dsg1
Dsg3
17
Q
Dsg: Also strongly expressed in squamous cell carcinomas and other head and neck cancers, where it has been proposed as a potential molecular target for therapy
A
Dsg3
18
Q
Dsg: Major desmoglein isofrom in most simple and transitional epithelia, as well as cardiac myocytes
A
Dsg2
19
Q
Dsg: Prominent in desmosomes of the hair follicle, testis, and prostate
A
Dsg4
20
Q
Dsc: Largely limited to skin and oral epithelia
A
Dsc1
21
Q
Dsc: More widely expressed in most desmosome-containing epithelia and is the only desmocollin isoform in cardiac tissue
A
Dsc2
22
Q
Dsc: Most strongly expressed in stratifies squamous epithelia of the skin and oropharynx
A
Dsc3
23
Q
Desmosomal cadherins have been reported to engage in both homopholic and heterophilic interactions, although _____ interactions likely form the basis of epidermal intercellular adhesions
A
Heterophilic
24
Q
Desmoglein 1 autoimmune target
A
PF
PV
IgA pemphigus (intraepidermal neutrophilic-type)
25
Desmoglein 1 genetic target
Striate PPK (AD)
26
Desmoglein 1 infectious target
SSSS
| Bullous impetigo
27
Desmoglein 2 genetic target
ARVC (AD)
28
Desmoglein 3 autoimmune target
PV
PNP
IgA pemphigus (intraepidermal neutrophilic-type)
29
Desmoglein 4 autoimmune target
PF
| PV
30
Desmoglein 4 genetic target
Hypotrichosis (AR)
| Monilethrix (AR)
31
Desmocollin 1 autoimmune target
IgA pemphigus (subcorneal pustular dermatosis-type)
32
Desmocollin 2 genetic target
ARVC (AR and AD)
33
Desmocollin 3 autoimmune target
PV
34
Desmocollin 3 genetic target
Hypotrichosis (AR)
35
Desmoplakin I/II autoimmune target
PNP
36
Desmoplakin I/II genetic target
Striate PPK (AD)
Carvajal syndrome (AR)
Lethal acantholytic epidermolysis bullosa (AR)
Skin fragility-wooly hair syndrome (AR)
37
Plakoglobin genetic target
Naxos disease
38
Plakophilin 1 genetic target
Skin fragility and ectodermal dysplasia (AR)
39
Plakophilin 2 genetic target
ARVC (AD)
40
Corneodesmosin genetic target
Hypotrichosis simplex of the scalp (AD)
41
Diffuse PPK
Wooly hair
Left ventricular cardiomyopathy
Carvajal syndrome
42
PPK
Wooly hair
Nail dystrophy
Skin fragility-wooly hair syndrome
43
Diffuse PPK
Wooly hair
ARVC
Naxos disease
44
Desmoglein 1 is also targeted by hyperactive serine proteases in
Netherton syndrome
45
Plakoglobin is expressed
Throughout all layers of the epidermis and is ubiquitously expressed in all epithelia
46
Desmoglein _____ immunoreactivity is due to cross-reactivity with desmoglein
1 in pemphigus sera
4
47
No epidermal phenotype in affected patients
Dsg2
| Dsc2
48
Directly bind to desmoplakin, and may also directly bind keratins and some desmosomal cadherins which is thought to aid in clustering and lateral stability of the desmosomal plaque
Plakophilins
49
Also known as gamma-catenin
Plakoglobin
50
Provides the major link between the keratin filaments and desmosomal plaque
Desmoplakin
51
Plakophilin _____ are both expressed throughout the epidermis, although plakophilin _____ is more predominant in basal compared to superficial epidermal keratinocytes
1 and 3
| 1
52
Plakophilin _____ is only expressed in the basal epidermal layer
2
53
Currently, there are no known human diseases associated with plakophilin
3
54
Envoplakin and periplakin are desmosomal plaque proteins expressed in the
Superficial layers of the epidermis
55
Envoplakin and periplakin autoantibodies are characteristic of _____ sera
Paraneoplastic pemphigus
56
Secreted glycoprotein that incorporates into corneodesmosomes and is also expressed in the inner root sheath of the hair follicle
Corneodesmosin
57
Ultrastructurally, basement membranes most offen appear as trilaminar structures, consisting of a central electron-dense region, known as the _____, adjacent on either side to an apparently less-dense area known as the _____
Lamina densa
| Lamina lucida
58
The absence of distinguishable _____ in tumor biopsies is used as an indicator of malignancy
Basement membranes
59
The DEJ can be divided into _____ distinct zones
3
60
3 zones of the DEJ
1. Keratin filament-hemidesmosome complex extending through the lamina lucida and lamina densa
2. Lamina densa
3. Sublamina densa
61
May result from shrinkage of the cell surface away from the lamina densa due to dehydration
Lamina lucida
62
The sublamina densa contains 2 readily distinguishable microfibrillar structures:
1. Anchoring fibrils
| 2. Microfibrils
63
Account for 40-65% of the total protein of the basement mebrane
Collage
64
Ubiquitous components of basement membranes
```
Collagen IV
Laminins
Nidogens
Heparan sulfate proteoglycans
Fibulins
```
65
Collagen IV is a heterotrimer of 3 alpha chains. The _____ chains are ubiquitous.
Alpha 1 and 2
66
The 6 chains of collagen IV are distributed in 3 major networks:
1. Alpha1-alpha2
2. Alpha3-alpha4-alpha5
3. Alpha1-alpha2-alpha5-alpha6
67
The chain compositions of collagen IV is determined by the
NC-1 domain
68
Collagen IV networks in the glomerular BM
Alpha1-alpha2
| Alpha3-alpha4-alpha5
69
Collagen IV networks in the smooth muscle BM
Alpha1-alpha2
| Alpha1-alpha2-alpha5-alpha6
70
Collagen IV networks in the DEJ
Alpha1-alpha2 (dominates)
| Alpha1-alpha2-alpha5-alpha6g
71
Mutations in the genes encoding the alpha _____ chains cause pathologies in different organs, ranging from eye, brain, and muscle defect to small-vessel disease, which often underlies ischemic strokes and intracerebral hemorrhages and to the HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome
1 and 2
72
Structural aberrations in the genes encoding the alpha _____ chains cause different forms of Alport syndrome
3, 4, 5 and 6
73
Alport syndrome is a genetic disease characterized by
Nephritis
| Deafness
74
The _____ chain is the antigen recognized by the circulating autoantibodies in the Goodpasture syndrome
Alpha3(IV)
75
Each laminin is a trimeric aggregate of _____ chain
1 alpha, beta and gamma
76
Major laminin of the epidermal BM
Laminin-5
| Now called laminin 332
77
Mutations in the _____ laminin chains underlie junctional EB
Alpha3, beta3, gamma2
78
Mutations in the _____ laminin chain cause congenital muscular dystrophy
Alpha2
79
Relatively small molecules which bind laminins at a specific site within the gamma1 and the gamma3 chain, but also collagen IV, perlecan and fibulins
Nidogens 1 and 2
80
These three proteoglycans are characteristically present in vascular and epithelial basement membranes:
1. Perlecan
2. Agrin
3. Collagen XVIII
81
Lack of _____ caused basement membrane deterioration in regions under increased mechanicsl stress, manifesting as lethal cardiac abnormalities and skin blistering
Perlecan
82
Major heparan sulfata proteoglycan of neuromuscular junctions and renal tubular basement membranes
Agrin
83
Considered to be a hybrid collagen-proteoglycan in various organs
Collagen XVIII
84
Transmembrane heparan sulfate proteoglycans present on most cell types, including basal keratinocytes of the epidermis
Syndecans
85
Family of highly conserved, calcium-binding extracellular matrix proteins
Believed to function as intermolecular bridges that stabilize supramolecular organization of extracellular matrix molecules, such as elastic fibers and basement membranes
Fibulins
86
Genetic defects of the genes encoding fibulin 4 and 5 cause different forms of
Cutis laxa
87
The 230-kDa bullous pemphigoid antigen 1, or BP230 is a protein with homology to _____, which bind intermediate filaments
Plakins
88
Major component of the hemidesmosomal inner dense plaque
BP230
89
Ablation of BP230 is associated with
Epidermolysis bullosa simplex
90
Major antigen in bullous pemphigoid
180-kDa bullous pemphigoid antigen 2 or BP180
91
180-kDa bullous pemphigoid antigen 2 or BP180 is a transmembrane collagen known as
Collagen XVII
92
Mutations in collagen XVII cause
Junctional epidermolysis bullosa
93
Plectin, another _____ homolog, is also a component of the hemidesmosome
Plakin
94
Mutations of _____ result in epidermolysis bullosa simplex with progressive muscular dystrophy and, in some cases, epidermolysis bullosa with pyloric atresia
Plectin
95
One key component of the hemidesmosome is the _____. It has a high affinity for laminin 332 and is essential to integration of the hemidesmosome with the underlying basement membrane
Integrin alpha6beta4
96
Mutations in either alpha6 or beta4 chains result in
Junctional epidermolysis bullosa associated with pyloric atresia
97
A member of the widely expressed cell surface transmembrane proteins of the tetraspanin family, _____, is also a component of the hemidesmosome. It forms complexes with alpha3beta1 and alpha6beta4 integrins at the basolateral surface of basal keratinocytes and stabilizes their functions
CD151
98
In addition to the expression of _____ in several tissues like the kidney and the skin, its gene also encodes the MER2 blood group antigen on erythrocytes
CD151
99
_____-negative patients presented with hereditary nephritis, sensorineural deafmess, pretibial epidermolysis bullosa, and beta-thalassemia minor
MER2
100
In addition to the hemidesmosomal components, other adhesion molecules are known to be present at the basolateral aspect of basal keratinocytes, for example, _____, the receptor for the laminin 332-311 complex in the basement membrane between the hemidesmosomes, and another transmembrae collagen, type _____
Integrin alpha3beta1
| XIII
101
Mutations in the _____ gene cause a rare systemic disorder with interstitial lung disease, nephrotic syndrome, and epidemolysis bullosa
Integrin alpha3
102
Disorder with skin blistering in infancy, progressive poikiloderma, sun sensitivity, and skin cancer
Kindler syndrome
103
Mutation in Kindler syndrome
Kindlin-1
104
The anchoring filaments contain _____ and the ectodomain of _____, 2 ligands that interact with each other
Laminin 332
| Collagen XVII
105
The major alpha3-containing laminin in the lamina densa between hemidesmosomes is probably the
Laminin 332-311 complex
106
The N-termini of laminin 322 bind to _____, the main component of the anchoring fibrils in the sublamina densa that, in turn, binds tightly to ______ containing fibrils so that anchoring filaments and fibrils are connected to each other and to the dermis
Collagen VII
| Collagen I
107
Major component of the anchoring fibrils
Collagen VII
108
The collagen _____ molecule is distinguished from other collagens in that it has a very long triple-helical domain, 450 nm in length
VII
109
Anchoring fibrils are further stabilized by tissue _____, which catalyzes the formation of covalent crosslinks
Transglutaminase
110
In the acquires form of epidermolysis bullosa, epidermolysis bullosa aquisita, and in bullous systemic lupus erythematosus, autoantibodies target mainly the
NC-1 domain of collagen VII
111
Mutations in _____, the gene encoding _____, result in dystrophic epidermolysis bullosa
COL7A1
| Collagen VII
112
Collagen, a family of 28 different collagen types, are the most abundant proteins in the dermis and represent _____% of its dry weight and _____% of its volume
75
| 20-30
113
All collagens have a basic structure of
3 alpha-chains, which have glycine as every third amino acid
114
In the dermis, the classic, cross-branded fibrils recognizable in the electron microscope contain collagen
I, III, V, XII, and XIV
115
In contrast, collagen _____ polymerizes into microfibrils
VI
116
Other collagens are needed to provide cohesion of the epidermis or the vascular structures with the dermal extracellular matrix, for example, collagens _____ in the epidermal basement membrane or collagens _____ in the vascular basement membrane zone
VII, XIII, XVII, XXIII
| VIII, XV, XVIII
117
Provides dermal elasticity
Elastin
118
Elastin molecules are rich in repetitive (hydrophilic/hydrophobic) sequences and are highly crosslinked
Hydrophobic
119
Elastic fibers can be stretched by _____% or more, and still return to their original form
100
120
Main componenrs of elastic fibers
Elastin (90%)
| Microfibrils
121
Negativelg charged polysaccharides that can bind large amounts of ions and water
Glycosaminoglycans
122
Four different proteoglycan-bound glycosaminoglycans are known
1. Chondroitin sulfate
2. Dermatan sulfate
3. Keratan sulfate
4. Heparan sulfate
123
Major proteoglycan in the dermis
| Associated with elastic fibers and forms huge complexes with hyaluronic acid, which provides the skin with its tautness
Versican
124
Ubiquitous glycosaminoglycan without protein core, a giant polysaccharide composed of N-acetylglucosamine/glucuronic acid disaccharides
Hyaluronic acid
125
Majro heparan sulfate proteoglycan of basement membranes that can sequester and present growth factors to their receptors
Perlecan
126
Hybrid collagen/proteoglycan found in epidermal and vascular basement membranes in the skin
Collagen XVIII
127
Small leucine-rich proteoglycans
Multiple functions:
-Bind to collagen fibrils and regulate their assembly
-Bind TGF-beta
-Connected to immune reactions by signalling through toll-like receptors
Decorin
| Biglycan
128
Transmembrane and glypicans membrane-anchored heparan sulfate proteoglycans
Control cell adhesion to the matrix and interact with multiple extracellular proteins, including growth factors, and thereby regulate cell functions
Syndecans
