1. Epithelia Gwen V. Childs, Ph.D. Graduate Microanatomy This presentation will probably involve audience discussion, which will create action items. Use PowerPoint to keep track of these action items during your presentation In Slide Show, click on the right mouse button Select “Meeting Minder” Select the “Action Items” tab Type in action items as they come up Click OK to dismiss this box This will automatically create an Action Item slide at the end of your presentation with your points entered.

2. Common features of epithelia Cells are connected to one another providing a lining for a surface or a hollow organ or tube Sit on a layer of fine filaments, called a "basal lamina". Form a boundary between the external environment and the remainder of the organ. Control movement of substances into and out of that organ.

3. How are epithelia classified? Depends on number of layers One layer Simple Two or more layers Stratified Pseudostratified Multilayered nuclei

4. Classification depends on shape Flattened, scale-like Squamous Cells are cubesCells are columns Cuboidal Columnar lumen

11. Transitional Epithelium (Bladder)

12. Pseudostratified Columnar epithelium

13. Importance of cell shape Flattened, squamous cells Reduced surface for passive transport across cells Can be stacked to provide protective layers Taller, cuboidal or columnar cells often express structural and functional polarity Apical surface functions Basal/lateral surface functions Absorption secretion Water and ion transport Enzyme actions receptivity secretion junctions Ion transport communication sensory

14. Importance of layering Protect against friction and injury Multilayered epithelia: Lower layers regenerate upper layers Barrier to water, disease some toxins, etc Single layered epithelia: Important in regulated transport of cells/molecules Communication/gateway

15. Key cell structures at each surface Microvilli, Cilia, Stereocilia Specialized junctions (Cellular interdigitations) Basal lamina + receptors

16. Increase surface area of cells 15-30X; Covered by glycocalyx; enzymes important in absorption are associated with this region

17. Core Actin filaments

18. Actin filaments are held in bundles by actin-binding proteins: fimbrin, villin, or fascin Actin filaments are held at the tip of microvilli by amorphous anchoring proteins; capping prevents depolymerization Actin is bound to myosin along lateral walls

19. Terminal Web Base of microvillus Microvillus actin binds to more actin running horizontally. Underneath the actin filaments are cytoskeletal filaments, also running horizontally Terminal web actin is cross-linked by spectrin.

20. Cilia Nine microtubule doublets surround a central pair Doublets connected by Dynein arms that walk along adjacent microtubule Nexin spokes radiate inward, connecting the doublets to the central pair

21. Specialized Microvilli Stereocilia are long microvilli Found in absorptive/secretory cells in epididymus (non-motile) Also found on special sensory cells in ear (cochlea) –Bending is a stimulus for sound or position sensation.

22. Cilia/flagellar functions Move egg down fallopian tube Move Sperm Move mucous in respiratory tract. Olfactory epithelium –Bear receptors that bind chemicals –This receptor binding is the stimulus for smell

23. SEM view of cilia and microvilli

24. Can you classify this tissue?

25. What kind(s) of junction(s) are in stratified squamous epithelium?

26. Anchoring junctions at the lateral surface Bind cells together via special ligands and their cytoskeletal systems –ligands are cadherins Junction differentiated by type of microfilament –Actin: adherent junctions –Intermediate filaments: desmosomes

27. Anchoring junctions : Desmosomes Like a spot weld or button. –Formed by a dense intracellular plaque on each side into which keratin filaments are looped. (desmoplakins; plakoglobin; 75 kD polypeptide; desmoglein) –Cadherin molecules (“calcium dependent adhesion molecules”) extend across the extracellular space to bind the cells together. (Desmocollins-I, II & desmogleins)

28. Desmosome Two dense plaques: one on each cell membrane Cadherins connect the two plaques via homophilic binding Cadherin binding requires Calcium Intermediate filaments loop into plaque

29. Adherent junctions Two dense regions one on each cell membrane (alpha actinin) Cadherins connect the two plaques via homophilic binding Cadherin binding requires Calcium Actin connects with dense regions on membrane

30. Pemphigus: skin disease Patients make antibodies against one of their desmosomal cadherans. Antibodies bind to desmosomal sites (only in skin and oral mucosa) disrupt connection between skin cells. Body fluid leaks into epithelial cells and causes blistering. Can be fatal if left untreated

31. Penphigus vulgaris

32. Penphigus Vulgaris Skin lesion histology: –Notice that the separation occurs in that layer where the desmosomes are abundant.

33. Can you classify this epithelium?

34. Junctional complex Tight (occluding) junctions –Zonula occludens Zonula adherans (belt-like zone) Desmosome Found frequently in columnar-type epithelia Prevents entry between cells and helps to maintain cell polarity

36. Microvilli

37. Occluding junction

38. Gap Junction

40. Specializations at the basal surface Basal/Lateral interdigitations Hemidesmosomes –Interactions between intermediate filaments and basal lamina Focal contacts –Interactions between actin filaments and basal lamina

41. Basal/Lateral Interdigitations Cells sit on multiple processes (like an octopus). These processes interdigitate with one another. Greatly increase surface area. Process filled with mitochondria On membrane are Na/K pumps (ATPase’s) (important for active transport of sodium and water conservation)

43. Anchoring junctions: Hemidesmosomes Like a half desmosome at the base of the cells links to basal lamina –A plaque anchors intermediate filaments inside the cell--ends are buried in plaque (contains desmoplakin-like protein). –anchoring proteins called “integrins”, bind from the keratin molecules inside to laminins in the basal lamina. (Integrins are receptors for specific extracellular matrix proteins). Bind like “velcro”

44. Anchoring junctions at the basal surface Bind cells to extracellular matrix –ligands are integrins Junction differentiated by type of microfilament –Actin: focal contacts –Intermediate filament: hemidesmosome

45. Dense plaque (desmoplakin) Cytoskeletal filaments (intermediate) anchored to plaque Integrin molecules: Transmembrane receptors for extracellular matrix proteins (fibronectins, laminins, etc) found in basal lamina fibronectin Plasma membrane Basal lamina

46. Thickened area on membrane Actin filaments anchored to plaque Integrin molecules: Transmembrane receptors for extracellular matrix proteins (laminins) found in basal lamina laminin Plasma membrane Basal lamina

47. What are integrins? Extracellular matrix receptors in the cell membrane: –Affinity relatively low (Ka= 10 6 --10 9 liters/mole): Why would that help the cell? –Depends on extracellular divalent cations (Ca++ or Mg++) –binding activates signalling cascades Composed of two glycoprotein subunits: alpha and beta. Combination and types of subunits may dictate selectivity of binding.

48. How do integrins function, in general? Regulated adhesion via integrins controls route and movement of cells in the body. Could you apply this to wound healing?