summary of dej junction and disease related to it.

1. Dr. Usha Chandra
EPIDERMAL
AND
EPIDERMAL-
DERMAL ADHESION

2. INTRODUCTION
 Proteins located on cell surface involved in
binding with other cells or with the extracellular
matrix (ECM)
 Epidermal integrity is required for
protection/resistance of the entire organism
against
- mechanical
- physical
- microbial insult.

3.  These receptors are composed of-
1. Intracellular domain that interacts with the
cytoskeleton
2. Transmembrane domain
3. Extracellular domain that interacts either with
other CAMs of the same kind (homophilic
binding) or with other CAMs or the extracellular
matrix (heterophilic binding)

4. Epidermal adhesion
 DESMOSOMES ( or macula adherenes) are
major cell adhesion.
 It is 3 dimension scaffolding of proteins that
extend from cell surface.

5. DESMOSOMES
 It anchors appoasing keratinocytes cell surface
membrane to intracellular keratin filament
network.
Cadheri
ns
desmogleins
desmocollin
Armadill
o
plakoglobulin
plakophillin
Plakins
desmoplakin
envoplakin
periplakin

6. Cadherins
 Extracellular part–
Amino terminal
Interface between cells.
 Intracellular part—
10-20nm from plasma membrane
form outer dense plaque.

7. Cadherins

8. DESMOGLEINS
dsg 1—
Superficial epidermis.
Squamous stratified
epithelium of skin
Orophynx, thyumus
Bullous impetigo
Staphylococcus scalded
skin syndrome
Icthyosis with netherton
syndrome.
Pemphigus foliaceus.
Muco cutaneous pemphigus
vulgaris.
Paraneoplastic pemphigus

9. dsg 2—
Basal /suprabasal
epidermis.
Transitional epithelium,
myocytes
Arrhythmogenic right
venticular cardiomyopathy

10. dsg 3—
Basal/ suprabasal
epidermis.
Squamous stratified
epithelium of skin
Orophynx, thyumus
Pemphigus vulgaris.
Paraneoplastic pemphigus

11. dsg 4—
Superficial epidermis.
Hair follicle , testis
prostrate
Pemphigus vulgaris.
Pemphigus folieaceus.
Cross reactivity with dsg1

12. DESMOCOLLINS
Dsc 1-
 Superficial epidermis.
 Skin and oral epithelium.
Dsc 2—
 Cardiac tissue.
 Down regulation in colorectal carcinoma.
Dsc 3—
 Stratified squamous epithelium of skin and oropharynx.
IgA
pemphigus(subcorneal
pustural dermatosis)
Arrhythmogenic right
ventricular cardiomyopathy
Pemphigus(vegetative)

13. Armadillo

14. PLAKOGLOBULIN/ ϒ catenin —
 Bind to cytoplasmic tail of desmoglein, desmcollin “a”
isoform.
 Other domain bind to desmoplakin.
 Naxos disease(AR): wooly hair, diffuse palmoplantar
keratoderma, ARVC.
PLAKOPHILIN—
 Function not clear.
 Bind to desmoplakin , keratin.
PP1 Ectodermal dysplasia.
PP2 ARVC

15. DESMOPLAKIN 1 and 2
 Is member of hemidesmosome protein .(BPAG1 ,
Plectin , envoplakin , periplakin).
 Amino terminal plakoglobulin.
 Carboxyl terminal keratin.
Striated PPK (AD)
Carvajal Syndrome(AR) : diffuse PPK , wooly hair ,
left ventricular cardiomyopathy
Lethal acantholytic epidermolysis bullosa

16. Dermo – Epidermal Junction

17. INTRODUCTION
 Complex form of basement membrane .
 Underlie epithelial & endothelial cells which separate
them from each other or from the adjacent connective
tissue stroma.
 Interface between the dermis & epidermis.
 It is continuous with the junction between dermis &
epidermal appendages.
 The complexity & heterogeneity of DEJ can be
appreciated only at electron microscopic level

18. STRUCTURE
50-90 nm

19. Functions of basement
membrane
 Templates/support during repair, differentiation and
restoration.
 Sites of attachment for cell layers or for cells to their
underlying matrix.
 Substrates for the programmed migration and
selective interactions of germ layers in development.
 Permeability barriers .(heparan sulphate)
 Protection of attached cell types from apoptosis.
 The anchoring complex and responsible for the
stability of epithelial-stromal attachment.
 Obstacle to cell migration.

20. Ultrastructure of DEJ

21. DEJ
1ST ZONE
Keratin filament –
hemidesmosomal
complex
2ND ZONE
Lamina densa
3RD ZONE
Sub basal lamina

22. First zone
 Lamina lucida upto lamina densa
 Lamina lucida is considerd as result from
shrinkage of cell surface away from lamina
densa due to dehydration.

23. Keratin intermediate filament-
7 to 10 nm.
Basal cell to desmo/hemidesmosomes.
Anchoring filament- 2 – 8nm
Plasma plasma
membrane to basement membrane.

24. Second zone(lamina densa)
 Electron- dense amorphous structure.
 20-50 nm .
 At high magnification  granular fibrous
appearance.
 Account for 40 -65% of total basement
membrane proteins.
 Major proteins component is type IV collagen,
nidogen, perlecan ,laminin.

25. Third zone( basal lamina)
 Contains microfibrillar structures.
 Anchoring fibrils--
Primarily type VII collagen.
Condensed fibrous aggregates , 20 - 75 nm in diameter
( absent in basement membrane of blood vessels
,smooth muscles).
At high resolution nonperiodic , random, cross-striated
banding pattern (stained of collagen).having frayed end

26.  Proximal end the basal lamina,
 Distal end fibrous network of the dermis.
 Many of anchoring fibril originated
and loops back into lamina densa.
 Other inserted their distal ends into
anchoring plaques (electron-dense
amorphous-appearing structures
completely independent of lamina densa)

27.  Microfibrils—
Contain fibrillin.
10-12 nm
Elastin related fibre extent from papillary dermis
to basal lamina.

28. Ubiquitous Components of
Basement Membrane
Type IV collagen
Laminin
Nidogen/Entactin
Heparan sulfate proteoglycan

29. Type IV collagen
 Heterotrimer of 3 alpha chain--
N terminal cystein rich (7s) domain.
Central triple helical domain.
C –terminal globular chain.
Alpha1 and alpha 2 are ubiquitous
Alpha 3/4/5/6 are restrited distributed.

30. Laminin
 It is hetrotrimetric molecule, where each laminin
isoform consisting of
 alpha chain.
 Beta chain.
 Gamma chain.
 Long arm ~ 125 nm
 Short arms are variable(largest measures ~80 nm)

31.  The globular & rodlike domains of laminin have
been individually implicated in various functions
including
 Cell attachment & spreading. ( BIND INTEGRIN)
 ADHESION
 Migration
 Polarity.

32. Nidogen / Entactin
 Glycoprotein with dumbbell configuration.
 It is attached to one of the short arms of
laminin at the gamma 1 chain forming a stable
complex.
 Nidogen alone as well as laminin- nidogen
complex specifically bind to type IV collagen.
 Nidogen is localized to the L.D. of basement
membrane & along the adjacent cell surface

33. Heparan sulfate proteoglycan
 Perlecan
 Agrin
 Collagen XVIII
 Syndecans are transmembrane HSPG have affinity
for laminin.
 Provide architecture , polarity, signaling,adhesion.

34. FIBULINS
 Ca binding extracellular matrix proteins.
 Stablize intermolecular bridges .
 genetic defect fibulin 4 and 5 cause cutis laxa.

35. Epithelial-Specific
Basement membrane
Components
Hemidesmosome
Anchoring filaments
Anchoring fibrils & anchoring plaques

36. Hemidesmosome (HD)
 It is closely resembles ½ of the desmosome but
distinct structures/immunology.
 BPAG1 ~~desmoplakin.
mutation epidermolysis bullosa simplex.
 BPAG2-- k/a XVII collagen.
intracellular ligand– plectin and BPAG1 and β4
extra-cellular ligand– alpha 6 , laminin 332.
Mutation  junctional epidermolysis bullosa.

38.  Plectin— HD-1 antigen--
Mutation causing loss of plectin  Epidermolysis
bullosa simplex.
Progressive
muscular dystrophy
 Integrin alpha6 beta4—
high affinity for laminin 5 .
Essential to integration of HD with underlying basement
membrane & stroma.
Mutation  junctional epidermolysis bullosa with pyloric
atresia.

40. Thank you