lecture 13: epithelial tissues – an overview Flashcards

1
Q

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

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do epithelial tissues undergo regeneration?

A
  • from stem cell pools
  • e.g. intestinal crypt, hair-follicle bulge, corneal limbus, mammary gland terminal end bud
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why focus on epithelial stem cells?

A
  • important roles in regenerative medicine
  • e.g. utility in being able to treat burns patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

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

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are tight junctions?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Of what do tight junctions form barriers to diffusion?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are tight junctions formed?

A
  • a meshwork of sealing strands of transmembrane proteins (claudin, occludin)
  • focal connections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are anchoring junctions?

A
  • allow the cytoskeleton to adhere to the ECM or other cells
  • include:
    • adherens junctions (connect to actin filaments)
    • desmosomes, hemidesmosomes (connect to indermediate filaments)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Of what do anchoring junctions consist?

A
  • an intracellular plaque that attaches to the cytoskeleton
  • transmembrane proteins that bind to adjacent proteins on other cells/ECM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are features of adherens junctions?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the main features of desmosomes?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are features of hemidesmosomes?

A
  • 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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do adherens junctions do?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is one of the functions of adherens junctions?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do cadherins bind?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens during the process of compaction?

A
  • 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
Q

How can expression of cadherins cause cell sorting?

A
  • 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
Q

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

A
  • 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
Q

What are some members of the cadherin superfamily?

A
  • 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
Q

What do desmosomes do?

A
  • 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
Q

How do desmosomes link to the intracellular filaments?

A
  • 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
Q

What is the function of hemidesmosomes?

A
  • 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
Q

How do hemidesmosomes link to cytokeratin filaments?

A
  • 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
Q

Apically to basally, what cell junctions are found?

A
  • 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
31
What is EMT?
* epithelial to mesenchymal transition * can also have MET * when epithelial cells receive specific signals they can break the adhesions between cells, loosen the grip on the ECM without undergoing apoptosis, released from basement membrane * e.g. development of neural crest cells, gastrulation * important in development of tissues and organs: * cutaneous structures, limb, gut organs, foregut and respiratory associated organs, kidney, tooth
32
What does EMT generate?
* cells with properties of stem cells * driving expression of Snail or Twist (mesenchymal inducers) in human mammary epithelial cells causes them to take on stem cell characteristics * intestinal epithelial stem cells express mesenchymal markers * e.g. highly upregulated expression of fibronectin (mesenchymal cell marker) * formation of mammospheres * self-renewing spheres * don't entirely understand why yet * pseudomesenchymal state * if these proteins have a role in maintenance/proliferation and movement of stem cells, might understand why tumours are so dangerous
33
review points:
* what is the difference between epithelial and connective tissues? * what are characteristics of epithelial tissues? * what is an occluding junction (tight junction)? * what are anchoring junctions (desmosomes, hemidesmosomes, adherens junctions)? * what is the basal lamina? * what regulates polarity of epithelial cells? * what is the epithelial to mesenchymal transition (EMT)? * why is it suggested that epithelial stem cells have mesenchymal properties?