Cell adhesion Flashcards

1
Q

What do epithelial tissues do?

A

Line body surfaces, tubes and cavities

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2
Q

What is the main stress bearing component of epithelial tissue?

A

Cytoskeletons

Linked by cell-cell and cell-matrix junctions

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3
Q

What is the main stress bearing component of connective tissue?

A

Extracellular matrix

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4
Q

What is epithelial tissue supported by?

A

Basement membrane

Connective tissue

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5
Q

What is a typical connective tissue cell?

A

Fibroblast

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6
Q

What are the 3 characteristics that classify epithelia?

A

Number of cell layers
Shape of cells
Surface specialisations

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7
Q

What are the different classifications based on cell layers?

A

Simple
Pseudostratified
Stratified

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8
Q

What are the different classifications based on cell shape?

A

Squamous
Cuboidal
Columnar

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9
Q

What are the different classifications based on specialisations?

A

Keratinised

Microvilli

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10
Q

What does the apical surface of epithelial cells connect to?

A

Nothing, it is always free

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11
Q

What morphology do epithelial cells have?

A

Polarised

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12
Q

What is the basal surface of an epithelial cell attached to?

A

Basement membrane

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13
Q

What do tight junctions distinguish between?

A

The apical domain

The basolateral domain

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14
Q

What is meant by the barrier and fence function of tight junctions?

A

Barrier - no movement of macromolecules through paracellular pathway
Fence - no movement of proteins in the membrane between the two domains

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15
Q

Name the 4 kinds of cell-cell junctions found on the lateral membrane

A

Tight junction
Adherens junctions
Desmosome
Gap junction

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16
Q

Name the 2 kinds of cell-matrix junctions found on the basal membrane

A

Hemidesmosome

Focal adhesion

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17
Q

Which junctions interact with keratin?

A

Desmosomes

Hemidesmosomes

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18
Q

Which junctions interact with actin filaments?

A

Tight junctions
Adherens junctions
Focal adhesions

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19
Q

Name the roles of the 6 junctions

A
Tight junctions - barrier and fence
Adherens junctions - adhesions
Desmosomes - adhesion
Gap junctions - communication
Hemidesmosomes - adhesion
Focal adhesions - adhesion
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20
Q

What is adhesion vital for maintaining?

A

Tissue integrity

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21
Q

What does the cytoskeleton consist of?

A

Intermediate filaments
Microfilaments
Microtubules

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22
Q

What is the role of cytoskeleton?

A

Cell migration
Cell division
Maintaining tissue integrity

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23
Q

What are the three main intermediate filament proteins?

A

Keratin
Vimentin
Desmin

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24
Q

How many keratin genes are there?

A

over 40

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25
What is the subunit of keratin?
Heterodimer
26
What are keratin intermediate filaments assembled from?
A dimer of type 1 and type 2 keratin
27
What are the cells of the epidermis?
Keratinocytes Melanocytes Langerhans cells
28
The epidermis prevents two things, what are they?
Loss of water | Entrance of microbes
29
How often is the epidermis renewed?
10-20 days
30
What are TA cells?
Transit amplifying cells
31
What keratin variations make up the basal layer?
K5 | K14
32
What keratin variations make up the top layers?
K1 | K10
33
What is the role of a desmosome?
Mediate cell cell adhesion | Anchor keratin intermediate filaments to membrane
34
Which non epithelial tissues express desmosomes?
Meninges of the brain | Heart muscle
35
What are the components of a desmosome?
Desmosomal cadherins (Desmocollins, desmogleins) Plakoglobin Plakophilin Desmoplakin
36
Where are desmocollins and desmogleins found?
In the space between the two plasma membranes
37
Where is plakoglobin found?
Attached to the desmosomal cadherins and to plakophilin
38
Where is desmoplakin found?
Attached to plakoglobin/plakophilin and then also attached to the keratin filaments
39
How many desmocollins genes are there?
3
40
How many desmogleins genes are there?
4
41
Where are the different desmosomal cadherins expressed?
In the upper layers it is mostly variaition 1 | In the lower layers it is mostly variation 3
42
What is pemphigus?
An autoimmune blistering disease caused by defective cell-cell adhesion
43
What are the two types of pemphigus?
Pemphigus foliaceus | Pemphigus vulgaris
44
What causes the two variations of pemphigus?
Pemphigus foliaceus - DSG1 | Pemphigus vulgaris - DSG3
45
What are the symptoms of pemphigus foliaceus?
Blistering in the upper empidermis Epidermis remains largely intact Prognosis is good
46
What are the symptoms of pemphigus vulgaris?
Blistering occurs in the lower epidermis Epidermis is severely compromised Prognosis is poor Almost always fatal if untreated due to fluid loss and infection
47
What is the role of a hemidesmosome?
Mediate cell-extracellular matrix adhesion Found at the basal surface of basal layer cells Anchor keratin intermediate filaments to the membrane Interact with ECM components laminin and collagen
48
Describe the basemement membrane
``` Underlies all epithelial tissues 40-120nm thick Not penetrated by blood vessels Composed of laminin 5 and collagen 4 Synthesised by epithelial cells ```
49
Describe laminin
Consists of three chains, alpha, beta and gamma Contains binding domains for cells and collagen Contributes to organising the matrix and helping cells attach to it
50
Describe collagen
Most abundant protein in mammals 3 collagen alpha chains are wound around each other to form a triple helical structure These are assembled into larger fibres
51
How is a hemidesmosome composed?
Three membrane spanning proteins One protein in the basement membrane 2 proteins in the cell
52
What are the three membrane spanning proteins?
BPAG2 Alpha6 Beta4
53
What is the protein in the basement membrane?
Laminin5
54
What are the two proteins in the cell?
BPAG1 | Plectin
55
What are intermediate filaments attached to?
BPAG1 | Plectin
56
What are collagen filaments attached to?
Laminin5
57
What is epidermolysis bullosa?
A genetic blistering disease of the skin caused by defective cell-ECM adhesion
58
What are the three types of epidermolysis bullosa?
Epidermolysis bullosa simplex Junctional epidermolysis bullosa Dystrophic epidermolysis bullosa
59
What is EB simplex?
Epidermis separation | Caused by keratin 5/ keratin 14/ BPAG1/ plectin/ alpha 6 or beta 4 mutation
60
What is junctional EB?
Separation at the basal membrane | Caused by laminin 5/ BPAG 2 /alpha 6 or beta 4 mutations
61
What is dystrophic EB?
Tissue separation at the upper dermis | Caused by collagen 7 mutation
62
What does EB simplex look like?
Mild blistering | Localised to hands and feet
63
What does junctional EB look like?
At birth large amounts of skin are blistered Poor prognosis Large internal involvement Mortality of 87% in first year
64
What does dystrophic EB look like?
Repeated blistering and scarring throughout life Characterised by joint contractures and fusions of the fingers and toes Increased risk of squamous cell carcinoma
65
Describe an adherens junction
Mediate cell-cell adhesion Found in simple and stratified epithelia Anchor actin filaments to the membrane
66
What is the composition of an adherens junction?
Classical cadherins Beta catenin or plakoglobin Alpha catenin
67
Where is the actin cytoskeleton found in the epithelial cell?
Around the periphery | The actin cortex
68
What attaches to the actin filament?
Alpha catenin
69
What are cadherins?
E-cadherin is expressed in epithelia cells There is also, N, P and VE versions Single pass transmembrane glycoproteins
70
How are cadherins arranged in an adherens junction?
Arrayed in parallel | "adhesion zipper"
71
What strengthens the adhesion of cadherins?
Calcium
72
What is the role of cadherins in morphogenesis?
Appearance and disappearance of specific cadherins drives morphogenesis E.g neurulation
73
Describe what cadherins do in neurulation
Epithelial cells of the embryonic ectoderm lose expression of E-cadherin and acquire N-cadherin Neural tube forms N-cadherin becomes cadherin 7 allowing breakaway from neural crest Re-expression of n-cadherin so that peripheral ganglia can form
74
What is epithelial mesenchymal transition?
The process whereby epithelial cells lose normal characteristics and gain new characteristics
75
What may an EMT result in?
Loss of histological structure Increased motility Increased invasiveness (cancer)
76
How does colorectal cancer form?
Mutation of cadherin 1 gene
77
What does loss of E-cadherin promote?
Movement and metastasis
78
What are focal adhesions?
Mediate cell-matrix adhesion | Anchor actin filaments to the membrane
79
What are focal adhesions comprised of?
Integrins Structural proteins Singalling proteins
80
What attaches to the actin filament?
The structural and signalling proteins
81
What do interns attach to?
Matrix proteins
82
Name some structural proteins found in focal adhesions
``` Talin Paxillin Filamin Alpha actinin Vincilin ```
83
Name a signalling protein found in focal adhesions
Focal adhesion kinases
84
What are integrins?
Heterodimers | Composed of 2 non covalently linked subunits
85
What is the difference between active and inactive integrins?
Inactive conformation is tightly folded | Change triggered by binding to ligand or to talin
86
What is outside-in signalling?
Cells come in contact with ECM proteins Integrins bind and switch on Recruit talin Form mature focal adhesion complex
87
How are focal adhesions involved in cell migration?
They form at the leading edge (lamellipodium) attaching the leading edge to the substratum
88
What is inside-out signalling?
Platelets express integrin When they come into contact with thrombin, talin is activated Increases the affinity of integral for fibrinogen. Platelet plug is formed
89
What is glanzmann's disease?
Mutations in alphaIIb or beta3 causes defective clotting and excessive bleeding Cutaneous haemorrhages