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Intercellular Junctions

May 1, 2023

Resource Faculty: Dr. Ashish Shrestha Dr. Vinay Marla

Prepared By: Raman DhungelBDS 2014 , BPKIHS

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Objectives: We shall be discussing:about different types of intercellular junctionsabout the location of these junctionsabout the proteins and structural molecules involvedabout clinical abnormalities

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Contents: Introduction to intercellular junctionsClassificationFunctions Proteins involvedClinical significanceSummary & MCQs

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What are intercellular junctions? points of contact between the plasma membranes of adjacent cells.

consist of multi-protein complexes that provide contact between neighboring cells or between a cell and the extracellular matrix.

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Composition: Typically consist of three components: a transmembrane adhesive protein, a cytoplasmic adapter protein,&a cytoskeletal filament.

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Functions of intercellular junctions: Cell junctions may : - Form fluid-tight seal between cells. - Anchor cells together or to extracellular materials. - Allow ions/molecules to pass from cell to another cell within a tissue.

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Classification: 1. Occluding Junctions (Zonula occludens) 2. Adhesive/Anchoring Junctions a) Cell-to-cell

◦ i) Zonula adherens◦ ii) Macula adherens (Desmosome)

b) Cell-matrix◦ i) Focal adhesions◦ ii) Hemidesmosome

3. Communicating (Gap) Junctions

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Occluding/Tight junctionsclosely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid.

control the passage of material through the intercellular spaces (e.g., from the interstitium to the lumen of a gland).

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Occluding/Tight junctionsMost abundantly seen in apices of epithelial cellsFound only in vertebratesCan modify to form leaky junctions

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Anchoring junctions(cell to cell) -provide strength to the cell by mechanical attachment. Two types on the lateral cell surface: zonula adherens ,which interacts with the network of actin filaments inside the cell; and macula adherens or desmosome, which interacts with intermediate filaments.

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Structure of zonula

adherens Actin filaments of adjacent cells are attached to the

E-cadherin–catenin complex by -actinin and vinculin.The E-cadherin–

catenin complex interacts with identical molecules embedded in

the plasmamembrane of the

adjacent cell.

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Structure of Desmosome

Intracellular attachment plaque anchored with intermediate filaments

are seen. The extracellular

portions of desmocollins and desmogleins from opposing cells interact with each other in the localized area of the

desmosome, forming the cadherin “zipper.”

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Anchoring junctions (Cell to ECM)

Focal adhesions - anchor actin filaments of the cytoskeleton into the basement membrane (e.g. between a leucocyte and a vessel wall) & Hemidesmosomes (hemi, Gk.- half) anchor intermediate filaments of the cytoskeleton into the basement membrane.

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Focal AdhesionOn the cytoplasmic

side, the arrangement of different actin-binding

proteins are seen. These proteins interact with

transmembrane protein integrin , the extracellulardomains of which bind to

proteins of the extracellular matrix (e.g., fibronectin).

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Hemidesmosomes:Hemidesmosomes look like

half-desmosomes that attach cells to the underlying basement membrane.

Rather than using desmogleins,

hemidesmosomes use desmopenetrin cell adhesion proteins,which are members

of Integrin family.

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Gap junctions:clusters of intercellular channels that allow direct diffusion of ions and small molecules between adjacent cells.intercellular space narrows from 25 nm to 3 nm.first discovered in myocardium and nerves between adjacent cells because of their properties of electrical transmission

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Structure of a gap junction:-gap junction between

adjoining cells showing the structural components of the membrane that form

channels(connexons)

-formed by a circular array of six subunits, dumbbell-shaped transmembrane

proteins(connexins)

- connexons, have a central opening of about 2 nm in

diameter.

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Clinical Significance:Cell – cell and cell – matrix junctions have important role in differentiation, development & function of normal cells, tissues and organs.

However, function may be altered by genetic abnormalities of junctional or cytoskeletal proteins, or by autoimmune disease.

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Clinical Significance:Mutation of gene of desmosome, hemidesmosome and intermediate filament protein :i. Epidermolysis bullosaii.Blistering skin disorderMutation of gene of extracellular matrix proteins:i. Pemphigus vulgarisii.Pemphigus foliaceous

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Pemphigus Vulgaris - an autoimmune disease -antibodies against proteins Blistering disease of oral mucosa: antibodies against desmoglein-3 &

Skin: antibodies against desmoglein-1

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Clinical significance:

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Mutation in the gene encoding connexin-26 (Cx26) -congenital deafness.

Cx46 and Cx50 gene mutations- congenital cataractsbullous pemphigoid- presence of autoantibodies to collagen XVII (BP180) and BP230.

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Clinical Significance: Mutation of connexins may also cause:

Demyelinating disease (Charcot-Marie Tooth) Oculodentodigital dysplasia –ODD syndrome

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Summary: 1. Occluding Junctions (Zonula occludens) 2. Adhesive/Anchoring Junctions a) Cell-to-cell

◦ i) Zonula adherens◦ ii) Macula adherens (Desmosome)

b) Cell-matrix◦ i) Focal adhesions◦ ii) Hemidesmosome

3. Communicating (Gap) Junctions

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@ZAMIn

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MCQ 1. Junction that prevents two cell compartments from mixing is:A. gap junctionB. desmosomesC. tight junctionD. cell junction

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MCQ 2. Pore- like connections between adjacent cells is an example ofA. cell junctionB. desmosomesC. tight junctionD. gap junction

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MCQ 3. Which of the following is a cell adhesion molecule A. Lysin B. MyosinC. IntegrinD. Keratin

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MCQ 4. Tight junctions:A. are essential for metabolic couplingB. don’t occur in vertebratesC. have the closest approach of two plasma

membranes of any junctionD. surround connexons

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MCQ 5. Hemi desmosome differs from spot desmosome in that hemi desmosome: A. connects cell to cell B. connects extracellular matrix to

extracellular matrix C. connects cell to extracellular matrixD. has tonofilament , made up of intermediate

filament

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References:

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