1
Intercellular Junctions
May 1, 2023
Resource Faculty: Dr. Ashish Shrestha Dr. Vinay Marla
Prepared By: Raman DhungelBDS 2014 , BPKIHS
©RAMAN 2016
May 1, 2023 2
Objectives: We shall be discussing:about different types of intercellular junctionsabout the location of these junctionsabout the proteins and structural molecules involvedabout clinical abnormalities
©RAMAN 2016
May 1, 2023 3
Contents: Introduction to intercellular junctionsClassificationFunctions Proteins involvedClinical significanceSummary & MCQs
©RAMAN 2016
May 1, 2023 4
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.
©RAMAN 2016
May 1, 2023 5
Composition: Typically consist of three components: a transmembrane adhesive protein, a cytoplasmic adapter protein,&a cytoskeletal filament.
©RAMAN 2016
May 1, 2023 6
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.
©RAMAN 2016
May 1, 2023 7
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
©RAMAN 2016
May 1, 2023 8 ©RAMAN 2016
May 1, 2023 9
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).
©RAMAN 2016
May 1, 2023 10
Occluding/Tight junctionsMost abundantly seen in apices of epithelial cellsFound only in vertebratesCan modify to form leaky junctions
©RAMAN 2016
May 1, 2023 11
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.
©RAMAN 2016
May 1, 2023 12
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.
©RAMAN 2016
May 1, 2023 13
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.”
©RAMAN 2016
May 1, 2023 14
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.
©RAMAN 2016
May 1, 2023 15
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).
©RAMAN 2016
May 1, 2023 16
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.
©RAMAN 2016
May 1, 2023 17
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
©RAMAN 2016
May 1, 2023 18
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.
©RAMAN 2016
May 1, 2023 19
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.
©RAMAN 2016
May 1, 2023 20
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
©RAMAN 2016
May 1, 2023 21
Pemphigus Vulgaris - an autoimmune disease -antibodies against proteins Blistering disease of oral mucosa: antibodies against desmoglein-3 &
Skin: antibodies against desmoglein-1
©RAMAN 2016
May 1, 2023 22
Clinical significance:
©RAMAN 2016
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.
May 1, 2023 23
Clinical Significance: Mutation of connexins may also cause:
Demyelinating disease (Charcot-Marie Tooth) Oculodentodigital dysplasia –ODD syndrome
©RAMAN 2016
May 1, 2023 24
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
©RAMAN 2016
May 1, 2023 25 ©RAMAN 2016
@ZAMIn
May 1, 2023 26 ©RAMAN 2016
May 1, 2023 27
MCQ 1. Junction that prevents two cell compartments from mixing is:A. gap junctionB. desmosomesC. tight junctionD. cell junction
©RAMAN 2016
May 1, 2023 28
MCQ 2. Pore- like connections between adjacent cells is an example ofA. cell junctionB. desmosomesC. tight junctionD. gap junction
©RAMAN 2016
May 1, 2023 29
MCQ 3. Which of the following is a cell adhesion molecule A. Lysin B. MyosinC. IntegrinD. Keratin
©RAMAN 2016
May 1, 2023 30
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
©RAMAN 2016
May 1, 2023 31
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
©RAMAN 2016
May 1, 2023 32
References:
©RAMAN 2016
May 1, 2023 33 ©RAMAN 2016