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Cell Adhesion and Communication Flashcards

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1
Q

What is epithelial tissue?

A

Tissue covering the surfaces of internal and external organs. All share the same basic structure: a layer of cells ontop of a basement membrane.

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2
Q

What type of epithelial tissue is found at alveoli?

A

Simple squamous epithelium

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3
Q

What type of epithelial tissue is found in the kidney?

A

Simple cuboidal epithelium

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4
Q

What type of epithelial tissue is found in the intestine?

A

Simple columnar epithelium

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5
Q

What type of epithelial tissue is found in the oesophagus?

A

Stratified squamous epithelium

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6
Q

What type of epithelial tissue is found in the respiratory tract?

A

Pseudo-stratified ciliated columnar epithelium

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7
Q

Name the 3 classes of cell-adhesion junctions:

A
  1. Occluding junctions
  2. Attachment junctions
  3. Communication junctions
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8
Q

What are occluding junctions?

A

Cell-adhesion junctions that form an impermeable layer between epithelial cells.
-Tight Junctions

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9
Q

What are attachment junctions?

A

Cell-adhesion junctions that link to cytoskeleton, to actin and to intermediate filaments of adjacent cells and to the extracellular matrix.

  • Adherens junctions
  • Desomosomes
  • Hemidesmosomes
  • Focal Adhesions
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10
Q

What are communication junctions?

A

Cell-adhesion junctions that directly connect cytoplasm of adjacent cells.
-Gap Junctions

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11
Q

Name the types of cell-cell adhesions

A
  1. Tight Junctions
  2. Adherence Junctions
  3. Desmosomes
  4. Gap Junctions
  5. Non-Junctional Adhesions
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12
Q

Name the types of cell-matrix adhesions.

A
  1. Hemidesmosomes
  2. Focal Adhesions
  3. Non-Junctional Adhesions
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13
Q

Describe the structure of occluding/tight junctions.

A

Bands of interconnected strands of integral membrane proteins encircling the cell. Lateral plasma membranes of cells are joined together through these sealing strands.

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14
Q

What are the three different types of sealing strands?

A
  1. Occludins
  2. Claudins
  3. JAMs (Junctional Adhesion Molecules)

All attach stably to numerous structural proteins to interconnect sealing strands.

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15
Q

What are claudins?

A

Core sealing strand proteins in tight junction fibrils

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16
Q

What are the function of claudins?

A

To allow passage of size/charge dependant molecules

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17
Q

How do claudins establish specificity?

A

Different claudins arrange their extracellular loops differently for different specificity pores

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18
Q

How many claudins have been found in humans?

A

24

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19
Q

Describe the possible effect of mutations in Claudin 16

A

Mutations of Claudin 16, expressed in the ascending limb of the loop of Henle, is associated with famial hypomagnesemia, hypercalciruia and nephrocalcinosis

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20
Q

What are the roles of Occludins and JAMs?

A

To provide positional stability in tight junctions

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21
Q

Sealing strand proteins are able to bind to signalling proteins. True or False?

A

True - they bind transiently.

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22
Q

What is paracellular transport?

A

Transfer of substances across an epithelium by passing through the intercellular space between the cells.

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23
Q

The different specificities of claudins allow tight junctions to regulate paracellular transport. True or False?

A

True

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24
Q

What is transcellular transport?

A

Transfer of substances across an epithelium through cells, through apical and basolateral membranes.

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25
Describe the process of glucose absorption across intestinal epithelium.
Active process of transcellular transport uses ATP to pump Na+ out of the cell across basolateral membrane through ATPase Na+/K+ pump against concentration gradient. Inside cell now therefore low [Na+], concentration gradient exists from apical to basolateral membrane Glucose enters cell through Na+/Glc symporter and pass through cell down concentration gradient into bloodstream through GLUT2 transport on basolateral membrane.
26
Explain how apical and basolateral membranes of cells can maintain their own identity?
Tight junctions prevent diffusion of proteins and lipids between the two, maintaining the unique identity of each membrane. In the context of glucose absorption, it is critical that the GLUT2 and Na+/K+-ATPase proteins are on the basolateral and Na+/Glc symporter on the apical.
27
How do adherens junctions appear on electron micrographs?
As thick dark bands near the plasma membrane of adjacent cells
28
What are adherens junctions?
A type of attachment junction that connects that actin cytoskeleton of adjacent cells
29
What are desmosomes?
A type of attachment junction that connects intermediate filaments of adjacent cells
30
What are the similarities between adherens junctions and desmosomes?
Both establish connections between cells Both bridged by rod-like structures that project in to the extracellular space
31
What are the best characterised type of adherens junctions?
Zonula adherens
32
What are zonula adherens?
Adherens junctions lying just beneath tight junctions in epithelial tissues. Other types of adherens depend on cell type.
33
What two properties do adherens junctions share regardless of location?
1. Share transmembrane receptor proteins - cadherins - which bind to identical cadherins on neighbouring cells. 2. Link to actin cytoskeleton and regulate changes in cell shape and/or resistant to sheer stress.
34
What is the role of desmosomes?
To add structural integrity by linking cytoskeletal intermediate filaments together
35
How do desmosomes appear under an electron micrograph?
Thick patches of electron dense material on cytosolic side of plasma membrane connected to IMFs in each cell.
36
Which cadherins do desmosomes contain?
Desmocollins, desmogleins and desmoplakin
37
What is the role of desmosomal cadherins?
Desmocollins and desmogleins link intermediate filaments through integral membrane proteins. They bridge intracellular space and serve as docking sites for cytosolic proteins. Desmoplakin binds IMFs linking desmosomes to the cytoskeleton.
38
What are hemidesmosomes?
Junctional cell-matrix adhesions connecting cells to underlying matrix.
39
What are the roles of hemidesmosomes?
Provide structural stability to epithelial sheets, linking extracellular matrix to IMFs through integrins.
40
Where are hemidesmosomes located?
On basal surface of epithelial tissues
41
How do hemidesmosomes anchor epithelial cells to the basement membrane (the “underlying matrix”)?
Through cytoplasmic plaques that connect to IMFs. Plaques composed of integrins and the adaptor protein plectin. Extracellular region interacts with components of the basement membrane.
42
How do hemidesmosomes interact with desmosomes?
Hemidesmosomes are orientated perpendicular to desmosomes, forming a robust network of IMFs that resist different types of mechanical stress
43
Severe blistering diseases can be a result from mutations in which junction structures?
Desmosomes and Hemidesmosomes
44
Hemidesmosomes look like half a desmosome and link to IMFs, like desmosomes, but are very different structurally. True or False?
True.
45
What are the non-junctional adhesion proteins?
Transmembrane receptors that facilitate cell-cell and cell-matrix adhesions; cell-adhesion molecule that facilitate the formation and/or organisation of junction components indirectly.
46
What are integrins?
A family of cell adhesion proteins that link the actin cytoskeleton to the substrate through focal adhesions.
47
Describe the structure of integrins.
Comprised of alpha and beta subunits, that each associate non-covalently to form a heterodimeric receptor.
48
Where are integrins expressed?
Virtually all animal cells
49
How is specificity of integrins mediated?
Composition of various alpha and beta subunits (18 a and 9 b known to form 24 different integrin dimers) As beta-1 is common in many integrins from alpha-1-alpha-7 and alpha-V, variation of alpha subunits helps define ligand specificity.
50
Cells only express one type of integrin. True or False?
False. Different cell types express different integrins depending on the component on the extracellular matrix its binding to. Their expression profile can change during development and different physiological conditions.
51
What ligands are able to bind the integrins?
Collagens, laminin, fibronectin, VCAM-1, etc…
52
Aspartate is a common amino acid of integrin ligands. True or False?
True. Currently unable to predict the integrin binding site based on the amino acid structure of the ligand but aspartate is common; binding to ECM components through Arg-Gly-Asp (RGD) site on ECM ligand is well characterised.
53
What is the common integrin binding motif?
Arg-Gly-Asp/RGD
54
Integrins can participate in inside-out as well as outside-in signalling. True or False?
True
55
Describe the events that take place to form blood clots.
- Platelets bind to ECM proteins and clotting factors, which is regulated. - GPCRs/RTKs activated when blood-clotting required. - Signalling cascades lead to activation of talin adaptor protein. - Talin adaptor protein links integrins to actin cytoskeleton in focal adhesions. - When talin is bound a conformational change in the extracellular domain occurs so that it binds to the substrate forming bloodclots.
56
Describe how integrins can partake in outside-in signalling
-Cell binds to ECM clustering integrins together. -Clustering of cytosolic domains form a docking site for signalling molecules that bring about changes inside the cell. E.g. cell differentiation, proliferation, apoptosis, cell migration, protein synthesis, gene regulation, cell polarity, actin organisation, contractility and endogenous tension.
57
Explain how integrins can regulate cell movement.
Endocytosis of integrins break attachments to substrates, and recycling establishes new attachments in the direction of cell movements.
58
Describe how integrin trafficking is affected in the formation of metastatic cancers.
Integrin is trafficked to the lysosome where it is degraded after recycling. If the pathway to the lysosome is overactive, the cell loses attachment and metastasis occurs.
59
What are Gap junctions?
A type of communication junctions that facilitate direct transfer of ions and small molecules between adjacent cells. They can also facilitate transmission of electrical signals between cardiac cells in muscle contraction.
60
Gap junctions are the only known method of direct communication between cells. True or False?
True. They are found in most vertebrates and invertebrates.
61
Describe the visualisation of Gap Junctions
Visualised as regions where adjacent plasma membranes are closer together than surrounding areas. Bridged by channels that project out of the plasma membrane.
62
Describe the structure of Gap Junctions.
A Gap junction is made of two connexon hemichannels, one in each membrane, that dock together in the intracellular gap. Gap junctions can form gap junction clusters of various sizes.
63
Describe the structure of connexons
Comprised of 6 connexin protein subunits, tetraspan integral membrane proteins with four transmembrane domains. Six connexins come together to form a heximeric complex, the connexon, with a pore of 2-4nm diameter.
64
Gap Junctions have different permeability properties depending on the connexins present. What are the three types of connexins?
1. Homomeric/homotypic 2. Heteromeric 3. Heterotypic
65
What are some functions of gap junctions?
Reflex reactions in the brain mediated by neurones linking by gap junctions allowing action potential to propagate rapidly avoiding chemical synapse Synchronisation of cardiomyocyte signals to contract, communicated through gap junctions.
66
Arrythmia can arise as a result from mutations in which type of cell-cell adhesion structure?
Gap junctions.
67
Explain how and why Gap Junctions are regulated.
Gap Junctions alternate between open and close states, mediated by phosphorylation of connexins in response to calcium or intracellular pH changes. Cell damage causes calcium ion elevation within the cell and release of damaging metabolites. Gap junctions close in response to increased [Ca2+] to prevent damage to neighbouring cells.

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