seminar on intercellular junctions

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  2. 2. INTERCELLULAR JUNCTIONS Presented By: Dr. Mamta Singh PGT - I 2
  3. 3. INDEX Introduction Definitions Classification Tight junctions Adherens junctions Desmosomes Gap junctions Hemidesmosomes and focal contacts Cellular adhesion Summary 3
  4. 4. INTERCELLULAR JUNCTIONS Specialized junctions at specific sites on the contacting cell membrane. Also called as membrane junctions. Mediate 2 types of interactions: 1. Cell to cell 2. Cell to extracellular matrix Abundant in epithelial tissues. 4
  5. 5. Maintain the mechanical integrity of animal tissues. Build up the paracellular barrier of epithelia. Control the paracellular transport. Provide contact between neighbouring cells or between a cell and the extracellular matrix. 5
  6. 6. On the molecular level intercellular junctions consists of three components: 1. Transmembrane adhesive protein 2. Cytoplasmic adapter protein 3. Cytoskeletal filament 6
  8. 8. The specialized junctions may be further classified as follows: OCCLUDING JUNCTIONS Tight junctions (Zona Occludens) COMMUNICATING JUNCTIONS Gap junctions ANCHORING JUNCTIONS Adhesive junctions Cell-to-cell 1. Zonula adherens (adheren junctions) 2. Macula adherens (desmosome) Cell-to-matrix 1. Focal adhesions 2. Hemidesmosomes 8
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  10. 10. Definitions Adherens junctions: A junction that links cell membranes and cytoskeletal elements within and between cells, connecting adjacent cells mechanically. Tight junctions: A junction at which adjacent plasma membranes are joined tightly together. Gap junctions: Narrowed portion of intercellular space containing channels. Desmosomes: Cell structure specialized for cell to cell adhesion Hemidesmosomes : Link the cell to the basal lamina and, through additional extracellular molecules, to ECM. 10
  11. 11. TIGHT JUNCTIONS Tight junctions, or zonula occludens: Closely associated areas of two cells. Form a tight belt like adhesive seal. Selectively limits the diffusion of water, ions & larger solutes as well as migration of cells. Separating the interior of body from the external world. 11
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  13. 13. 13 In electron microscopic structure of thin sections of tight junctions the plasma membrane of adjacent cells appear to fuse together in a series of one or more contacts.
  14. 14. Two structural proteins have been identified in the structure of tight junctions namely: Occludins Claudin 14
  15. 15. A family of more than 20 proteins, called Claudins, constitutes the main structural proteins of tight junction strands. Claudins have four transmembrane sequences, but they are not related in sequence to occludin. 16
  16. 16. 17 A.Preliminary model of tight junction structure with claudin linking the two membranes together & peripheral protein ZO-1 linking the cytoplasmic tail of claudin to actin filaments. B-C. transmembrane topology of claudin & occludin.
  17. 17. Tight junctions Extracellular domains of claudins form rows of pores along tight junction. Each claudin has a unique selectivity for cations or anions. At the zona occludens the membranes of adjoining cells converge and are at a distance of 0.1- 0.3 m. 18
  18. 18. Human gingival keratinocytes (HGKs) were studied by means of freeze-fracture technique for the investigation of intercellular contacts. In vivo the tight junctions, which were of low complexity were co-distributed with desmosomes; in one case, the strands ran directly through desmosomal plaques. Where tight junctions and desmosomes occurred together, no gap junctions were seen. In contrast, where no tight junctions were present, gap junctions and desmosomes were co-localized. Meyle J, Gttig K, Rascher G and Wolburg H: Transepithelial electrical resistance and tight junctions of human gingival keratinocvtes. J Periodont Res 1999; 34: 214222 19
  19. 19. Adherens junctions and Desmosomes are two types of adhesive junctions using homophilic interactions of cadherins to bind epithelial cells to adjacent cells. 20
  20. 20. ADHERENS JUNCTIONS The zonula adherens is a band like specialization of the membrane and cytoplasm that encircles the apex of adjoining cells and strongly bonds the cells together. In this junction the opposing membranes are 15 20 nm apart . It is a major site of epithelial cell cohesion.
  21. 21. Adherens Junction Cytoplasmic actin filaments bind adherens junctions. Homophilic interactions between densely clustered E- cadherens (the epithelial transmembranic adhesive protein) bind adjacent cells together at adherens junctions. - catenin(cytoplasmic adapter protein) and Plakoglobin (desmosomal cytoplasmic adapter protein) bind the cytoplasmic domains of E-cadherin.
  22. 22. Adherens Junction An another cytoplasmic adapter protein, -catenin, binds cadherins to actin filaments and -catenin to actin filaments. Adherens junctions are first connections that are established between developing sheets of epithelial cells. The contact begins when cadherins on the tips of filopodia engage to the cadherins of another cell.
  23. 23. Adherens Junction Adherens junctions are a pre requisite for tight junctions that allow epithelial cells to establish polarity with proteins and lipids in plasma membranes. Zonula adherens is the major site for cell cohesion. It stabilizes the surface of epithelia. The junctions and polarity determine the orientation of mitotic spindle and the plane of division . This allows for asymmetrical division of stem cells (stratified epithelium).
  24. 24. Adherens junction In mature columnar epithelia a belt like adherens junction called zonula adherens encircles the cell near the apical surface thus maintaining physical integrity of the epithelium. 25
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  26. 26. DESMOSOMES Desmos means bound , Soma means body. It is also called Macula Adherens. Provide strong adhesion between the epithelial and muscle cells. These junctions are small disk shaped spot welds between adjacent cells. 27
  27. 27. Desmosomes Ist observed in the spinous layer of epidermis by an Italian pathologist Giulio Bizzazero. Helps to resist shearing force. Structure that forms the site of adhesion between 2 cells ,consisting of dense plate in each adjacent cells seprated by a thin layer of extracellular material. Desmosomes link 2 cells together. 28
  28. 28. Desmosomes Human Gingival Keratinocytes (HGK)s are interconnected on the cell periphery by Desmosomes. Consist of two dense attachment plaques into which tonofibrils insert and an intermediate, electron dense line in the extracellular compartment. 29
  29. 29. Desmosomes Cellular adhesions at desmosomes are mediated by transmembrane proteins: Desmogleins Desmocollins. Plakoglobin also called gamma- catenin. Molecular composition of desmosomes vary in particular tissues 30
  30. 30. Desmosomes Desmosomes are site for attachment, structural ability of epithelium linking cytoskeletal structures of two cells. Desmoglein -2 and desmocollin -2 are found in most of the desmosomes. The devlopment of animal tissues depends on desmosomes & their constituents proteins. 31
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  32. 32. GAP JUNCTIONS Gap junctions are plaque that contain large intercellular channels that connect the cytoplasm of a pair of cells. Half channels in each membrane are called connexons. Connexons consists of six protein subunits, called connexins. 33
  33. 33. Gap Junctions Connexin are named by their molecular weight. Found exclusively in chordates. Most connexons pair with identical connexons on the partner cell to form homotypic gap junctions. Gap junction communication is conditional It depends on: Number of channels Fraction that are open or closed 34
  34. 34. Gap Junctions Plants lacks gap junctions Cells in plant tissues maintain continuity through plasmodesmata. Molecules smaller than 1kd diffuse freely through plasmodesmata. 35
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  36. 36. Gap Junctions Oleamide- fatty acid amide produced by the brain , blocks gap junction and induce sleep in animals. Gap junctions allow osteocytes to maintain cellular supply line to acquire nutrients from distant blood vessels. White blood cells may also form transient gap junctions with endothelial cells. Cells in most metazoans communicate by gap junctions. 37
  37. 37. Gap Junctions Mutations in connexins genes cause human disease. Recessive mutation in the connexin -26 gene are most common cause of human Deafness. Mutation in connexin-32 gene causes degeneration of myelin sheets around axons. 38
  38. 38. HEMIDESMOSOMES 39 Basal Cells Tonofilaments Lamina lucida Lamina densa Anchoring filaments Anchoring fibrils Type IV collagen Proteoglycans 39 Hemidesmosomes
  39. 39. HEMIDESMOSOMES Hemidesmosomes are adhesive junction that link cytoplasmic filaments to basal lamina. Adhesion to extracellular matrix is different from intercellular adhesion because integrins provide transmembrane link between cytoskeleton and extracellular matrix. 40
  40. 40. Contd Two transmembrane proteins mainly found in hemidemosomes are 64 integrin and type XVII collagen. Outside the cell 64 integrin binds to laminin-5 in basal lamina. The extracellular collagen triple helix forms anchors filaments between membrane and basal lamina. 42
  41. 41. Contd STRUCTURE OF HEMIDESMOSOME: Adhesive protein INTEGRIN Cytoplasmic proteins PECTIN, BP 180 Cytoskeletal element - INTERMEDIATE FILAMENTS Target molecule - LAMININ. 43
  42. 42. CELLULAR ADHESION PRINCIPLES OF CELLULAR ADHESION 1. First principle of adhesion Cells define


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