lecture 13: epithelial tissues – an overview Flashcards Preview

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1

What is an epithelium and where do we see epithelial tissue?

  • cells in metazoans must associate to form organs 
  • in epithelial tissues the cytoskeletons of cells are linked 
    • epithelia are polarised tissues 
  • epithelial tissue often seen lining organs   
  • in connective tissue the extracellular matrix is the main stress-bearing component 
  • mechanical stresses are transmitted from cell to cell by cytoskeletal filaments anchored to cell-matrix and cell-cell adhesion sites 
  • extracellular matrix directly bears mechanical stresses of tension and compression 

2

How do epithelial tissues undergo regeneration?

  • from stem cell pools 
  • e.g. intestinal crypt, hair-follicle bulge, corneal limbus, mammary gland terminal end bud 

3

Why focus on epithelial stem cells?

  • important roles in regenerative medicine 
  • e.g. utility in being able to treat burns patients 

4

What are the four functional classes of cell junctions found in animal tissues?

  • anchoring junctions 
    • actin filament attachment sites
      • cell-cell junctions (adherens junctions)
      • cell-matrix junctions (actin-linked cell-matrix adhesions)
    • intermediate filament attachment sites 
      • cell-cell junctions (desmosomes) 
      • cell-matrix junctions (hemidesmosomes)
  • occluding junctions 
    • tight junctions (in vertebrates)
    • septate junctions (in invertebrates) 
  • channel-forming junctions
    • gap junctions (in animals)
    • plasmodesmata (in plants)
  • signal-relaying junctions 
    • chemical synapses (in the nervous system) 
    • immunological synapses (in the immune system) 
    • transmembrane ligand-receptor cell-cell signalling contacts (Delta-Notch, ephrin-Eph, etc.). Anchoring, occluding, and channel-forming junctions can all have signalling functions in addition to their structural roles 

5

What are tight junctions?

  • specialised junctions of epithelial/endothelial cells
  • aka occluding junctions 
  • they facilitate transcellular transport 
  • block free flow of molecules from one surface of the cell down to the other 
  • this means that the transport of molecules e.g. glucose is regulated - can't just diffuse down the sides of the cells, have to have particular transporters on the apical and basal membranes of the cell 
  • tight junctions also help define the apical and basolateral membranes of the cell → block free movement of proteins from one side of the cell membrane to the other 
  • i.e. tight junctions important in giving cells polarity 
  • most apical of the junctions 

6

Of what do tight junctions form barriers to diffusion?

  • solutes: we can see this using dye solutions 
  • membrane proteins: this tells us that newly synthesized proteins are directed to specific regions of the cell membrane 

7

How are tight junctions formed?

  • a meshwork of sealing strands of transmembrane proteins (claudin, occludin) 
  • focal connections 

8

What are anchoring junctions?

  • allow the cytoskeleton to adhere to the ECM or other cells
  • include:
    • adherens junctions (connect to actin filaments) 
    • desmosomes, hemidesmosomes (connect to indermediate filaments)

9

Of what do anchoring junctions consist?

  • an intracellular plaque that attaches to the cytoskeleton 
  • transmembrane proteins that bind to adjacent proteins on other cells/ECM 

10

What are features of adherens junctions?

  • cell-cell anchoring junction
  • transmembrane adhesion protein = cadherin (classical cadherin) 
  • extracellular ligand = cadherin in neighbouring cell 
  • intracellular cytoskeletal attachment = actin filaments 
  • intracellular anchor proteins = α-catenin, β-catenin, plakoglobin (γ=catenin), p120-catenin, vinculin, α-actinin 

11

What are the main features of desmosomes?

  • cell-cell anchoring junction 
  • transmembrane adhesion protein = cadherin (desmoglein, desmocollin)
  • extracellular ligand = desmoglein and desmocollin in neighbouring cell 
  • intracellular cytoskeletal attachment = intermediate filaments 
  • intracellular anchor proteins = plakoglobin (γ-catenin), plakophilin, desmoplakin 

12

What are features of hemidesmosomes?

  • cell-matrix anchoring junction
  • transmembrane adhesion protein: integrin α6β4, type XVII collagen (BP180) 
  • extracellular ligand: extracellular matrix proteins 
  • intracellular cytoskeletal attachment: intermediate filaments 
  • intracellular anchor proteins: talin, vinculin, α-actinin, filamin, paxillin, focal adhesion kinase (FAK) plectin, dystonin (BP230)

13

What do adherens junctions do?

  • form a continuous belt below the tight junctions, the zona adherens, in epithelial cells that bring actin filaments into alignment 
  • cadherins form the transmembrane linkages

14

What is one of the functions of adherens junctions?

  • myosin motors can cause contraction of bundles of actin filaments in adhesion belts – this results in cells to narrow at the apex and epithelia to form tubues 
  • sheet of epithelial cells
  • invagination of epitehlial sheet caused by an organized tightening of adhesion belts in selected regions of cell sheet 
  • epithelial tube pinches off from overlying sheet of cells
  • epithelial tube 
  • e.g. neural tube 

15

How do cadherins bind?

  • cadherins bind in a homophilic manner and binding is dependent upon calcium concentration 
  • e-cadherin is most common form of cadherin found in epithelial cells 
  • calcium binds to the flexible hinge regions to make them stiff therefore allowing binding 

16

What happens during the process of compaction?

  • cells of the early mouse embryo stick together weakly 
  • at the 8-cell stage they begin to express E-cadherin
  • as a result strongly adhere to one another 
  • roughly the same point at which totipotency is lost 

17

How can expression of cadherins cause cell sorting?

  • homophilic adhesion and differential expression of classical cadherins can cause cell sorting and is important in tissue formation 
  • can be seen in both two different types of cadherin being expressed and different levels of the same cadherin being expressed 
  • the latter may cause different tissue layers 
  • loss of a specific cadherin will disrupt formation of particular epithelial tissues  → e.g. loss of N-cadherin will prevent correct formation of the neural tube

18

What was an experiment demonstrating the sorting out and reconstruction of spatial relationships in aggregates of embryonic amphibian cells?

  • take epidermis + mesoderm → sort out so mesoderm is on inside and epidermis is on outside 
  • mesoderm + endoderm → sort
  • all three → something a lot like a normal embryo 
  • differential adhesion starts to form the tissue layers seen in the early embryo 

19

What are some members of the cadherin superfamily?

  • classical cadherins 
    • e-cadherin → many epithelia, adherens junctions, -/- = death at blastocyst stage; embryos fail to undergo compaction 
    • n-cadherin → neurons, heart, k/o die from heart defects 
    • p-cadherin → placenta; k/o abnormal mammary gland development 
    • ve-cadherin → endothelial cells; abnormal vascular development (apoptosis of endothelial cells)  
  • nonclassical cadherins 
    • desmocollin → skin, desmosomes, blistering of skin
    • desmoglein → skin, desmosomes, blistering skin disease due to loss of keratinocytes-cell adhesion 
    • t-cadherin
    • cadherin 23
    • fat (in drosphila)
    • fat1 (in mammals)
    • alpha, beta, and gamma protocadherins 
    • flamingo 

20

What do desmosomes do?

  • desmosomes "spot-weld" cells together to distribute tensile forces
  • through desmosomes the intermediate filaments of adjacent cells are connected to form a continuous network of great strength 

21

How do desmosomes link to the intracellular filaments?

  • the sides of cytokeratin filaments interact with the cytoplasmic plaque that is attached to an adjacent cell via cadherin interactions
  • non-classical cadherins, desmoglein and desmocollin, transmembrane proteins that form homophilic interactions with proteins from adjacent cell 
  • intracellular plaque links transmembrane proteins to intermediate filaments 
  • intracellular plaque = desmoplakin, plakoglobin, plakophilin  

22

What is the function of hemidesmosomes?

  • in contrast to desmosomes, hemidesmosomes attach to the ECM (via integrins) and to the ends of cytokeratin filaments 
  • they are chemically and functionally distinct from desmosomes 

23

How do hemidesmosomes link to cytokeratin filaments?

  • utilise a specialised integrin (α6β4) to link cytokeratin filaments via plectin and dystonin anchor proteins to extracellular laminin 
  • link to ends of intermediate filaments 
  • defects → cotton wool babies 

24

Apically to basally, what cell junctions are found?

  • occluding junction
  • cell-cell anchoring hunctions 
    • adherens
    • desmosomes 
  • channel-forming junctions 
  • cell-matrix anchoring junctions 

25

What is the ECM?

  • the ECM is an organised meshwork of proteins and polysaccharides 
  • structural proteins include collagen and elastin 
  • cellular adhesion to the ECM depends upon:
    • adhesive ligands: laminin, fibronectin 
    • anti-adhesive ligands: tenascin, chondroitin sulfate proteoglycan 

26

What is the basal lamina?

  • the basal lamina is a specialised ECM that underlies all epithelia 
  • also found surrounding muscle and the glomeruli of the kidney  

27

What is a primary component of the basal lamina?

  • laminin 
  • adhesive ligand 
  • trimeric molecule - three seperate chains 
  • crucifix shaped molecule 
  • binds to integrins
  • meshwork → self-assembly 
  • binds to other components of ECM 

28

What is a model of the basal lamina?

  • grid meshwork type thing link to each other and the plasma membrane of the cell 

29

What molecules regulate formation of apico-basal polarity?

  • Par3, Par6: scaffold proteins that bind to each other and to aPKC (atypical protein kinase C) 
  • these proteins associate with the tight junctions and serve as binding sites for Cdc42 and Rac – organisers of the actin cytoskeleton 
  • Crumbs complex in apical side
  • scribble complex in basal side 

30

What does epithelial cell polarity involve?

  • actin polarization 
  • regulated protein trafficking to apical, lateral, and basal membranes 
  • regulated secretion and absorption 
  • regulated ion flow 
  • signalling via integrin attachment to the ECM – this can influence cell proliferation