OVERVIEW

* Examination of BMZ

* Structure of BMZ

* Origin of BMZ

* Function of BMZ

* Examples of Some diseases affecting BMZ

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* Basement Membrane

* Dermo – Epidermal Junction (DEJ)

* Basal lamina

* Basement Membrane Zone (BMZ)

THE BASEMENT MEMBRANE ZONE

* It is a critical interface between the epidermis and dermis and is a highly specialized structure that allows for communication between different cell types.

PAS-positive basement membrane.

EXAMINATION OF BMZ

* Relatively poorly demonstrated with eosin in H and E preparations.

* As all basement membranes, it stains strongly for Glycoproteins and mucopolysaccharides by Periodic acid schiff stain (PAS).

* It is also stained intensely with silver techniques.

* The complexity & heterogeneity of BMZ can be appreciated only at ELECTRON MICROSCOPIClevel.

The basement membrane zone (BMZ) integrates the epidermis with the underlying dermis. On electron microscopy, the BMZ has three layers: a central electron-dense region known as the lamina densa and two regions of lower electron density to either side of this central region.

Ultrastructure of basement membrane (×37,800). (1, hemidesmosome; 2, lamina lucida; 3, lamina densa; 4, sublamina densa; 5, melanin; 6, tonofilaments)

BMZKIF/Hemidesmosome complex(Basal keratinocyte)Lamina lucidaLamina densaSub lamina densa

KERATIN INTERMEDIATE FILAMENTS* Also called tonofilaments, it is comprising keratin

5&14.

* It is a fine filamentous structures maintain the intracellular architecture & organization of basal cells.

* They course through the basal cells & inserted into the desmosome & hemidesmosome.

ATOMIC MASS UNIT

* The unified atomic mass unit (symbol: u) or dalton(symbol: Da) is the standard unit that is used for indicating mass on an atomic or molecular scale(atomic mass).

* One dalton is approximately the mass of one nucleon(either a single proton or neutron) = 1.660538921(73)×10−27 kg.

HEMIDESMOSOMES (HD)

* Numerous electron-dense plates located in the lowerregion of the plasma membrane of the basal cells.

* It is closely resembling ½ of the desmosome seen in cell–cell junction but based on chemical criteria, these 2 structures appear to be immunologically distinctive.

* Characteristics of HD proteins has been aided by the use of auto-antibodies presented in serum samples of patients with bullous pemphigoid.

* As result of this, the antigens recognized by these sera identified proteins ranging in mass from 165-240 kDa.

* These proteins are immunologically & structurallydistinct.

* Monoclonal antibodies have been constructed to both intracellular & extracellular regions of HD.

BPAG1

* It is a homodimer with homology to desmosomaldesmoplakin.

* It is generally believed that it is the major componentof the HD inner dense plaque.

PLECTIN

* It is another dimeric desmoplakin homologue.

* Its tissue distribution is not limited to BMZ.

6 4 INTEGRIN

* They are large class of trans-membrane extra-cellular matrix binding proteins that provide cell attachment & subsequent signal transduction.

* It has a selective high affinity for laminin 5.

TYPE XVII COLLAGEN (BPAG2)

* 180 kDa

* It is an unusual trans-membrane prt.

Collagenous extra-cellulardomain interact with laminin 5

Intra-cellular domain interact mainly with BPAG1

LAMINA LUCIDA (LL)

* External to the plasma membrane

* 25-50 nm in width.

* Contains the anchoring filaments.

ANCHORING FILAMENTS

* Series of filaments traversing the lamina lucida from the epidermal basal cells & insert into the laminadensa.

* Several antigens forming anchoring filament proteins.

LAMININS

* Immunolocalized to basal lamina (= LL+LD).

* Numerous glycoprotein family with semirigid & extended structures.

* It is hetrotrimetric molecule, where each lamininisoform consisting of

alpha chain. Beta chain. Gamma chain.

* The 4 extremities of the crosslike structure contain globular domains, the 3 short arms contain extra domain, approximately 20 nm from their free end.

LAMININ 5

* Its general structure as laminin family.

* It has short arms comparing to other laminins.

* Its shape is consistent with its potential to be the anchoring filament protein.

* It has a high affinity for integrins.

* It also bind to the NC-1 domain of type VII collagen(the anchoring fibril protein).

LAMINA DENSA (LD)

* Appears as an electron-dense amorphous structure.

* 20-50 nm in width.

* At high magnification, it has a granular fibrousappearance.

* Account for 40-65% of total basement membraneproteins.

* Major proteins component is type IV collagen where it appears as a filament of variable thickness which is morphologically distinct from the collagen fibers in the subjacent dermis.

TYPE IV COLLAGEN

* Immunolocalized mainly to LD & also found in anchoring plaque.

* It has a structure closely related to the intracellularor procollagen form, typical of all members of the collagen protein family.

* The triple helical nature of the amino terminus of type IV collagen is unique & has been designated as the 7-S domain.

* Covalent interactions among 7-S domain of the type IV collagen are the basis for the specialized fiberform characteristic of basement membrane.

NIDOGEN

* It is a glycoprotein with dumbbell configurationlocalized to the LD.

* 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 complexspecifically bind to type IV collagen.

PERLECAN

* It is a Heparan sulfate proteoglycan.

* It consists of a core protein of various length with different numbers of covalently associated glycosaminoglycan chains.

* High sulfate content makes this molecule with highlynegative charge & hydrophilic.

* It swell with hydration & have a major role in determining which proteins or ions can transverse the lamina lucida & access the epidermal intracellular spaces.

SUB LAMINA DENSA

* It’s major component is anchoring fibrils which appear as condensed fibrous aggregates of type VIIcollagen.

ANCHORING FIBRILS

* Type VII collagen appears to have a major triple-helical domain is approximately 450 nm in length.

* Type VII collagen is synthesized & secreted as monomeric protein but rapidly dimerizes at the aminoterminals.

* These structures are proteolytically cleaved afterformation of the centrosymmetric dimer.

* The dimers then aggregates laterally to form the anchoring fibrils.

* The complex NC-1 domain binds to laminin 5 & also to components of the lamina densa.

* Many of the anchoring fibrils inserted their distalends into electron-dense amorphous-appearing structures completely independent of lamina densa, known anchoring plaques.

ANCHORING PLAQUES

* The anchoring plaques are electron-dense structurecomposed of type IV collagen & laminin.

* They are independent of lamina densa , & distributed randomly in the papillary dermis below lamina densa & are inter-related by additional anchoring filaments.

REFERENCES

* Adel A. Al-Ghamdi Dermatology Department King Fahd Hospital of university (Presentation).

* The Basement Membrane Zone- Making the Connection Vidal MD, AAD.

* Google images.

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