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
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
3
Q
Why focus on epithelial stem cells?
A
- important roles in regenerative medicine
- e.g. utility in being able to treat burns patients
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)
- actin filament attachment sites
- 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
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
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
7
Q
How are tight junctions formed?
A
- a meshwork of sealing strands of transmembrane proteins (claudin, occludin)
- focal connections
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)
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
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
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
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)
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
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
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
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
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
Q
What is the ECM?
A
- 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
Q
What is the basal lamina?
A
- the basal lamina is a specialised ECM that underlies all epithelia
- also found surrounding muscle and the glomeruli of the kidney
27
Q
What is a primary component of the basal lamina?
A
- laminin
- adhesive ligand
- trimeric molecule - three seperate chains
- crucifix shaped molecule
- binds to integrins
- meshwork → self-assembly
- binds to other components of ECM
28
Q
What is a model of the basal lamina?
A
- grid meshwork type thing link to each other and the plasma membrane of the cell
29
Q
What molecules regulate formation of apico-basal polarity?
A
- 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
31
Q
What is EMT?
A
- 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
