Cell adhesion Flashcards

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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
Q

What is the subunit of keratin?

A

Heterodimer

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26
Q

What are keratin intermediate filaments assembled from?

A

A dimer of type 1 and type 2 keratin

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27
Q

What are the cells of the epidermis?

A

Keratinocytes
Melanocytes
Langerhans cells

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28
Q

The epidermis prevents two things, what are they?

A

Loss of water

Entrance of microbes

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29
Q

How often is the epidermis renewed?

A

10-20 days

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30
Q

What are TA cells?

A

Transit amplifying cells

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31
Q

What keratin variations make up the basal layer?

A

K5

K14

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32
Q

What keratin variations make up the top layers?

A

K1

K10

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33
Q

What is the role of a desmosome?

A

Mediate cell cell adhesion

Anchor keratin intermediate filaments to membrane

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34
Q

Which non epithelial tissues express desmosomes?

A

Meninges of the brain

Heart muscle

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35
Q

What are the components of a desmosome?

A

Desmosomal cadherins (Desmocollins, desmogleins)
Plakoglobin
Plakophilin
Desmoplakin

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36
Q

Where are desmocollins and desmogleins found?

A

In the space between the two plasma membranes

37
Q

Where is plakoglobin found?

A

Attached to the desmosomal cadherins and to plakophilin

38
Q

Where is desmoplakin found?

A

Attached to plakoglobin/plakophilin and then also attached to the keratin filaments

39
Q

How many desmocollins genes are there?

A

3

40
Q

How many desmogleins genes are there?

A

4

41
Q

Where are the different desmosomal cadherins expressed?

A

In the upper layers it is mostly variaition 1

In the lower layers it is mostly variation 3

42
Q

What is pemphigus?

A

An autoimmune blistering disease caused by defective cell-cell adhesion

43
Q

What are the two types of pemphigus?

A

Pemphigus foliaceus

Pemphigus vulgaris

44
Q

What causes the two variations of pemphigus?

A

Pemphigus foliaceus - DSG1

Pemphigus vulgaris - DSG3

45
Q

What are the symptoms of pemphigus foliaceus?

A

Blistering in the upper empidermis
Epidermis remains largely intact
Prognosis is good

46
Q

What are the symptoms of pemphigus vulgaris?

A

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
Q

What is the role of a hemidesmosome?

A

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
Q

Describe the basemement membrane

A
Underlies all epithelial tissues
40-120nm thick
Not penetrated by blood vessels
Composed of laminin 5 and collagen 4
Synthesised by epithelial cells
49
Q

Describe laminin

A

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
Q

Describe collagen

A

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
Q

How is a hemidesmosome composed?

A

Three membrane spanning proteins
One protein in the basement membrane
2 proteins in the cell

52
Q

What are the three membrane spanning proteins?

A

BPAG2
Alpha6
Beta4

53
Q

What is the protein in the basement membrane?

A

Laminin5

54
Q

What are the two proteins in the cell?

A

BPAG1

Plectin

55
Q

What are intermediate filaments attached to?

A

BPAG1

Plectin

56
Q

What are collagen filaments attached to?

A

Laminin5

57
Q

What is epidermolysis bullosa?

A

A genetic blistering disease of the skin caused by defective cell-ECM adhesion

58
Q

What are the three types of epidermolysis bullosa?

A

Epidermolysis bullosa simplex
Junctional epidermolysis bullosa
Dystrophic epidermolysis bullosa

59
Q

What is EB simplex?

A

Epidermis separation

Caused by keratin 5/ keratin 14/ BPAG1/ plectin/ alpha 6 or beta 4 mutation

60
Q

What is junctional EB?

A

Separation at the basal membrane

Caused by laminin 5/ BPAG 2 /alpha 6 or beta 4 mutations

61
Q

What is dystrophic EB?

A

Tissue separation at the upper dermis

Caused by collagen 7 mutation

62
Q

What does EB simplex look like?

A

Mild blistering

Localised to hands and feet

63
Q

What does junctional EB look like?

A

At birth large amounts of skin are blistered
Poor prognosis
Large internal involvement
Mortality of 87% in first year

64
Q

What does dystrophic EB look like?

A

Repeated blistering and scarring throughout life
Characterised by joint contractures and fusions of the fingers and toes
Increased risk of squamous cell carcinoma

65
Q

Describe an adherens junction

A

Mediate cell-cell adhesion
Found in simple and stratified epithelia
Anchor actin filaments to the membrane

66
Q

What is the composition of an adherens junction?

A

Classical cadherins
Beta catenin or plakoglobin
Alpha catenin

67
Q

Where is the actin cytoskeleton found in the epithelial cell?

A

Around the periphery

The actin cortex

68
Q

What attaches to the actin filament?

A

Alpha catenin

69
Q

What are cadherins?

A

E-cadherin is expressed in epithelia cells
There is also, N, P and VE versions
Single pass transmembrane glycoproteins

70
Q

How are cadherins arranged in an adherens junction?

A

Arrayed in parallel

“adhesion zipper”

71
Q

What strengthens the adhesion of cadherins?

A

Calcium

72
Q

What is the role of cadherins in morphogenesis?

A

Appearance and disappearance of specific cadherins drives morphogenesis
E.g neurulation

73
Q

Describe what cadherins do in neurulation

A

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
Q

What is epithelial mesenchymal transition?

A

The process whereby epithelial cells lose normal characteristics and gain new characteristics

75
Q

What may an EMT result in?

A

Loss of histological structure
Increased motility
Increased invasiveness
(cancer)

76
Q

How does colorectal cancer form?

A

Mutation of cadherin 1 gene

77
Q

What does loss of E-cadherin promote?

A

Movement and metastasis

78
Q

What are focal adhesions?

A

Mediate cell-matrix adhesion

Anchor actin filaments to the membrane

79
Q

What are focal adhesions comprised of?

A

Integrins
Structural proteins
Singalling proteins

80
Q

What attaches to the actin filament?

A

The structural and signalling proteins

81
Q

What do interns attach to?

A

Matrix proteins

82
Q

Name some structural proteins found in focal adhesions

A
Talin
Paxillin
Filamin
Alpha actinin
Vincilin
83
Q

Name a signalling protein found in focal adhesions

A

Focal adhesion kinases

84
Q

What are integrins?

A

Heterodimers

Composed of 2 non covalently linked subunits

85
Q

What is the difference between active and inactive integrins?

A

Inactive conformation is tightly folded

Change triggered by binding to ligand or to talin

86
Q

What is outside-in signalling?

A

Cells come in contact with ECM proteins
Integrins bind and switch on
Recruit talin
Form mature focal adhesion complex

87
Q

How are focal adhesions involved in cell migration?

A

They form at the leading edge (lamellipodium) attaching the leading edge to the substratum

88
Q

What is inside-out signalling?

A

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
Q

What is glanzmann’s disease?

A

Mutations in alphaIIb or beta3 causes defective clotting and excessive bleeding
Cutaneous haemorrhages