CELL JUNCTIONS

INTRODUCTION DEFINITION CLASSIFICATION

-OCCLUDING JUNCTIONS -ADHESIVE JUNCTIONS a.cell-cell b.cell-matrix -COMMUNICATING(GAP) JUNCTIONS

MOLECULAR LEVEL OF INTERCELLULAR JUNCTIONS FUNCTIONS PATHOLOGIC CONSIDERATIONS CONCLUSION REFERENCES

When cells come into contact with one another,and sometimes with the extracellular matrix,specialized junctions may form at specific sites on the contacting cell membranes. These specialized junctions may be classified into several different categories :

1.OCCLUDING JUNCTIONS 2.ADHESIVE JUNCTIONS a.cell-to-cell: adherens junction desmosome b.cell-to-matrix: focal adhesions hemidesmosomes 3.COMMUNICATING(GAP) JUNCTIONS

Zonula=junction that completely encircles the cell(belt like) Macula= junction that is more circumscribed in content(spot like)

Fascia= junction that occupies only a patch/strip of the cell

surface Combinations: A junctional complex present b/w cells of a simple or pseudo stratified epithelium,usually consists of a tight junction,a zonula adherens & a desmosome Molecular level: 1.a transmembrane adhesive protein 2.cytoplasmic adapter protein 3.cytoskeletal filament

1.Occluding (tight) junction:

Unique to the epithelium Opposing cell membranes are held in contact by the presence of transmembrane adhesive proteins arranged in anastamosing strands that encircles the cell Intercellular space obliterated transmembrane adhesive proteins:include Occludin,members of Claudin family. cytoplasmic adapter proteins:

-cell polarity related proteins -vesicular transport related proteins -tumor suppressor proteins -transcription factor

cytoskeletal filament:Actin filament

The tightness of the junction correlated with the no of strands of transmembrane proteins E.g.:salivary gland secretory cells-2/3 strands;relatively permeable. salivary gland striated duct cell:6-9 strands;relatively impermeable to water Functions:
Control the passage of material thru the intercellular space A fence to define & maintain the 2 major domains of cell membranes,apical & basolateral surface

Currently accepted interpretation complementary/interacting protein particles of the 2 opposed cell membranes establish mutual contact & become interlocked across the intercellular gap like the teeth of a zipper Zonula Occludens:intestinal epi cells Fascia Occludens :endothelial lining of all the blood vessels except CNS

2.Adhesive junctions:
Hold cells together or anchor cells to the extracellular matrix. Intercellular space-20nm Epidermis,cardiac muscle as well

Functions:
Important in cellular signaling Their cytoplasmic components may interact with the cytoskeleton,triggering changes in cell shape or motility. They may act as nuclear transcription factor or co-activators

a. cell-to-cell adhesive junctions:

Principle transmembrane adhesive proteins - members of Cadherin family. cytoplasmic adapter proteins - members of Catenin family which interact with the cytoplasmic domain of transmembrane cadherin molecule,with the cytoskeleton and with other proteins 1.Zonula adherens: -The cadherin family member is E- cadherin - cytoplasmic adapter proteins are alpha and beta -cytoskeletal filament:actin filament

Other recently described transmembrane proteins:nectin,afadin,ponsin

lies a level just below zonula occludens.At a level just below these 2 parallel belt like junctions,spot like(macular) junctions are also present.Bcoz the belt like zonula adherens occupies the middle/intermediate position of junctional complex,it is referred to as an intermediate junction. Pri role is prevention of cell seperation during various contractile activities Maintenances of tension in the membrane

2.Desmosome:
The cadherins - desmoglobin and desmocollin.The interaction of these transmembrane proteins with those from adjacent cell results in a dense line in the middle of intercellular space at the desmosome The catenins - desmoplakin and plakoglobin which form an electron dense plaque which serves an attachment for the cytoskeletal components which in case of desmosome are intermediate filaments.

Bundles of tonofilaments are anchored to a disc like plaque. They resist the tensile forces Abundant in epi membrane that are adapted to withstand wear & tear E.g.:stratified squamous keratinizing epithelium

INTEGRINS are heterodimers of different alpha and beta subunits with specificity for various extra cellular matrix molecules. CADHERINS are calcium ion dependent proteins that interact homotypically with cadherins on the adjacent cell.

b.Cell-to matrix junctions:

structural organization similar to cell to cell adhesive junctions,but they use different molecular components & attach the cell to the extracellular matrix 1.Focal adhesions: Transmembrane component-member of the Integrin family. Cytoplasmic adapter proteins-actin binding proteins like alphaactinin,vinculin , talin .Link the transmembrane integrins to the Actin cytoskeleton

Binding of integrin to collagen,laminin,fibronectin & other extracellular matrix proteins results in recruitment & remodelling of actin cytoskeleton Also activates various intracellular signalling molecules 2.Hemidesmosomes: Link the basal surface of the epithelial cell to the basal lamina,& thru additional extracellular molecules,to the rest of the extracellular matrix. transmembrane adhesive proteins-integrins alpha6beta4,which binds specifically to the basal lamina glycoprotein laminin & collagenXVII(BP180) Cytoplasmic adapter proteins-bullous pemphigoid antigen 230 & plectin form a dense plaque on the cytoplasmic surface of the hemidesmosome,which functions as an attachment site for intermediate filaments

Integrin laminin 1 signaling interactions at the basal cell surface regulate cell polarization & cell differentiation programs in epithelial cells. Integrin-ligand mediated signaling mechanism might retard the onset of keratinocyte differentiation Act as rivets to distribute tensile/shearing forces thru an epithelium 3.Gap junctions:

Nexus Latin word for bond

Are plaque like regions of the cell membrane where the intercellular space narrows to 2-3 nm . Transmembrane adhesive proteins of the Connexin family form aqueous channels b/w the cytoplasm of the adjacent cell.6 connexin molecules form a connexon,which has a central channel of approximately 2nm diameter

The connexons in one cell, pair with connexons in the adjacent cell to create a patent channel Gap junctions electrically couple cells & allow for a coordinated response to a stimulus by the cells that are inter connected Do not form zonula,spot like Enables ions & small molecules including amino acids,sugars,nucleotides& steroids to pass directly from one cell to another Intracellular conc. of Ca regulates the permeability Also sensitive to pH changes

Plays a key role in conducting waves of depolarization thru out the heart in a pattern that brings about the contraction in the appropriate working sequence Hypo:vital role in relaying cell recognition signals,positional info or other signals required to direct the normal course of dev of embryo.

Occluding junction

occludin

occludin on the neighbouring cell

actin filaments

zonula occludens proteins

Gap junction

connexon

connexon on the neighbouring cell

actin filaments

Cell-cell & cell matrix junctions have important roles in the differential development & function of normal cells,tissues & organs. However, the functions of these junctions may be altered or disrupted by genetic abnormalities of junctional or cytoskeletal proteins or by auto immune diseases in which circulating antibodies to junctional proteins are present.

GENETIC DISORDER:
Mutations in 2 different Claudin genes recently have been identified as the bases for Hereditary Hypomagnesaemia & a form of Hereditary deafness Mutations of Connexin genes have been identified as the bases for Hereditary deafness,Congenital cataracts & a Demyelinating disease Dystrophic epidermolysis bullosa:abnormal collagen type7,weak anchoring fibrils Junctional epidermolysis bullosa:genetic mutation in laminin5, weak anchoring fibrils,weak epithelial c/t interphase.

-Enamel dysplasia is seen as ameloblasts fail to remain attached to enamel surface

Epidermolysis bullosa simplex:

- mutations in k5 &/or k14. -weakened filament bundles,plectin abnormalities- basal cells are less able to resist shearing forces -undergo cytolysis with blistering of the epidermis & oral mucosa.
Epidermolytic hyperkeratosis:

-mutation in k10 - affecting filament network of supra basal cells of cornifying superficial stratified epithelium. -cytolysis of upper level cells in the stratum spinosum leads to blistering of the epithelium as well as hyper proliferation of basal cells.

Mutations in keratins reduce the stress resistance of cells. After physically stretching cells that have mutations found in EBS (epidermolysis bullosa simplex) patients, the keratin filaments (green) start to break up and components of the cell junctions (red) begin to come apart.

Autoimmune disorders:
Cicatricial pemphigoid:auto antibodies to laminin 5 Bullous pemphigus: auto antibodies to BPAG-1 & BPAG-2

-detachment of keratinocytes & formation of sub epidermal blisters

Pemphigus vulgaris: auto antibodies to desmoglein 3 Pemphigus foliaceus:auto antibodies to desmoglein 1

-leads to desmosomal disruption & blister formation in skin & oral mucous membrane

Lichen planus:

Disruption of normal architectural association of collagen VII,integrin(alpha6 & beta 4)& anchoring filaments Cause is localized & chronic inflammation,initiated & maintained by an immune response to an unknown antigen Increased expression matrix metallo proteinase 2 is believed to result in basement membrane degradation
Oral squamous cell carcinoma:

demonstrates decreased expression of alpha 2 ,3,6 & beta 4. integrin subunit there by decreases their adhesion to basal laminae & enhancing their ability to invade c/t

CONCLUSION
cell junctions serve many purpose in addition to mechanical attachment; without em our bodies would disintegrate

REFERENCES:
MOLECULAR BIOLOGY OF THE CELL:ALBERTS,JOHNSON,WALTER;4TH ED;NY:GARLAND SCIENCE;2002 A TEXT BOOK OF HISTOLOGY:BLOOM & FAWCETT;2ND ED;NY:CHAPMAN & HALL;1994 ORAL HISTOLOGY:TEN CATES;5TH & 6TH ED; ST.LOUIS:MOSBY;2003 HAMS HISTOLOGY:DAVID H CORMACK;9TH ED;PHILADELPHIA:J B LIPPINCOTT COMPANY;1987 ORBANS ORAL HISTOLOGY & EMBRYOLOGY;18TH ED; NEW DELHI: CBS PUBLISHERS

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