Lecture 11 - The Extracellular Matrix Flashcards

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1
Q

All multicellular organisms have an

A

Extracellular matrix

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2
Q

The ECM supports

A

Cells

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3
Q

Different types of ECM control (6)

A
Cell adhesion
Signalling
Differentiation
Polarity
Division
Migration
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4
Q

During embryonic development, the ECM is integral to

A

Migration events that determine body polarity
Differentiation of stem cells
Reservoir of growth factors

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5
Q

How many types of matrix do animals have

A

Two

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6
Q

The interstitial matrix forms

A

Tissues and gives support to organs

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7
Q

The basal lamina

A

Underlies all epithelial cell layers

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8
Q

The two main macromolecules that form the ECM are

A
  1. Fibrous proteins (glycoproteins)

2. Polysaccharide chains (glycosaminoglycans)

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9
Q

What do glycosaminoglycans do

A

Link to core proteins to form proteoglycans

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10
Q

Variations in ECM composition cause

A

Diversity of materials to be formed

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11
Q

Calcified ECM forms

A

Bones and teeth

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12
Q

Soft transparent ECM forms

A

The cornea

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13
Q

The interstitial matrix is found in

A

Connective tissues

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14
Q

Which cell secretes the interstitial ECM?

A

Fibroblast cells

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15
Q

ECM molecules are synthesised

A

Intracellularly and then excreted by exocytosis

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16
Q

Once outside the cell, ECM molecules

A

Aggregate

to form a huge organised matrix

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17
Q

Chondrocytes form

A

Cartilage

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18
Q

Osteoblasts form

A

Bone

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19
Q

Collagen provides

A

Tensile strength in connective tissues

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20
Q

How many collagen genes do mammals have?

A

28

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21
Q

25% of protein mass in a mammal is

A

Collagen

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22
Q

Collagen is a very large macromolecule, so must be secreted in a precursor form called

A

Procollagen

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23
Q

Procollagen

A

Intracellular form of collagen that prevents aggregation

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24
Q

Procollagen is cleaved outside the cell which allows

A

Aggregation

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25
Q

What kind of helix is collagen?

A

Triple helix

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26
Q

Inside the cell, collagen is a

A

Triple helix

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27
Q

Outside the cell, collagen assembles into a

A

Fibril

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28
Q

Collagen fibrils assemble into collagen

A

Fibres

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29
Q

Collagen fibres lie

A

Criss crossed to provide strength

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30
Q

Collagen is

A

Post translationally processed

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31
Q

In the nucleus, collagen is

A

Transcribed from DNA > RNA > mRNA from the collagen gene

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32
Q

In the RER, collagen is

A

Translated into pre procollagen

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33
Q

Pre procollagen is labelled on the

A

N terminus to target it to the secretory pathway

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34
Q

Lysine residues on pre procollagen are

A

Hydroxylated

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35
Q

Hydroxylation of collagen is necessary for

A

O linked glycosylation

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36
Q

In the Golgi, pre pro collagen is

A

Hydroxylated
Glycosylated
Disulfide bonded

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37
Q

When the collagen leaves the Golgi, it is

A

Procollagen packed in secretory vesicles

38
Q

Once outside the cell, procollagen is

A

Proteolytically cleaved

39
Q

N proteinase cleaves the

A

N terminus of procollagen extracellularly

40
Q

C proteinase cleaves the

A

C terminus of procollagen extracellularly

41
Q

N and C proteinase cleavage allow

A

The higher order assembly of collagen

From fibrils to fibres

42
Q

Ehlers Danlos disease is a

A

Genetic disease that affects procollagen or procollagen processing enzymes

43
Q

In Ehlers Danlos, collagen fibrils do not

A

Assemble correctly (no criss crossing)

44
Q

Symptoms of ED (5)

A
  1. Bruising, stretchy skin
  2. Dislocation of joints, hyperflexibilty
  3. Arterial rupture
  4. Scoliosis
  5. Thin and fragile globe of eye
45
Q

ED type 6a has a defect in which gene?

A

Plod1

46
Q

Plod genes encode for

A

Lysyle hydroxylases

add OH to lysine in collagen

47
Q

Mutation in Plod1 results in

A

No hydroxylation of lysine in collagen

Therefore no O-linked glycosylation

48
Q

What resists compression and fills space in the interstitial ECM?

A

Polysaccharide and protein gels

49
Q

Proteoglycans are

A

Extracellular proteins linked to glycosaminoglycans (GAGs)

50
Q

Proteoglycans can have

A

Many GAG chains attached to them

51
Q

Proteoglycans and GAGs can form

A

Huge macromolecules resembling bottlebrushes

52
Q

Proteoglycans and GAGs form gels that combine with what to form an interstitial ECM?

A

Collagen

53
Q

The basal lamina anchors

A

Epithelial cells to the tissues underneath

54
Q

The basal lamina separates

A

Different connective tissue layers

55
Q

The basal lamina forms

A

A mechanical connection between layers of connective tissue

56
Q

The basal lamina can act as a

A

Selective filter

57
Q

In the kidney glomerulus, the basal lamina prevents

A

Blood and urine mixing

58
Q

The basal lamina is synthesised by

A

The cell layers on either side of it

59
Q

The basal lamina looks like

A

Mat like sheets

60
Q

Fibrillar collagen makes up the

A

Intersitial ECM

61
Q

Collagen type4 and laminin make up the

A

Basal lamina

62
Q

Nidogen and Perlecan

A

Cross link laminin and collagen type 4 together to hold the basal lamina together

63
Q

Laminin organises the

A

Basal sheet

64
Q

Laminin forms a

A

Triple helix part opens into 3 separate chains to form a ‘cross’

65
Q

How many laminin isoforms are there?

A

15

66
Q

The most abundant laminin in the body is

A

Laminin 511

67
Q

Many different protein isoforms suggest

A

Tissue specificity

68
Q

Laminin structure

A

Alpha, beta and gamma chains disulfide bonded chains
Self assembles
Long arm binds to cell surface receptors
Short arms join to other laminins

69
Q

Collagen 4 provides

A

Tensile strength
Triple helix
Procollagen
Self assembles

70
Q

Why can collagen 4 form a sheet?

A

Primary amino acid sequence of collagen 4

71
Q

GlyXY

A

Interrupted repeats of glycine confers bendiness to form a sheet

72
Q

Epidermolysis bulleosa is a

A

Genetic disease that forms blisters on the skin

Caused by failure in adhesion between dermis and epidermis

73
Q

During cell migration, focal adhesions form

A

At the cell front and disassemble at the back

74
Q

Focal adhesions are

A

Connections between the cell cytoskeleton and the ECM

Have receptors to confer specificity

75
Q

Focal adhesions provide

A
The force to move the cell
Signalling cues (matrix molecules and growth factors)
76
Q

Integrins are

A

Transmembrane receptors that couple the matrix to the cytoskeleton
Binding allows tension generation

77
Q

Integrin structure

A

Heterodimer

alpha + beta subunit

78
Q

Integrins link to actin via

A

Actin binding proteins (ABPs)

79
Q

Integrins signal

A

Mechanically and chemically

80
Q

Tensin, Talin and Vinculin

A

Form an adhesion complex with integrin that link the actin cytoskeleton to the ECM in a migrating cell

81
Q

Mature focal adhesions are

A

Dynamic multi protein complexes

82
Q

Integrins can signal

A

Bidirectionally

83
Q

When integrin is folded, it is

A

Inactive (does not bind to ECM or cytoskeleton)

84
Q

When integrin is unfolded, it is

A

Active (binds to ECM + cytoskeleton)

85
Q

Outside-in integrin signalling activates

A

A protein tyrosine kinase cascade

86
Q

Integrin signalling impacts (3)

A

Nuclear functions
RhoGTPases
Actin cytoskeleton: migration, spreading, polarity

87
Q

What are neural crest cells?

A

Cluster of stem cells at the top of the neural tube

88
Q

Downregulation of N-CAM in neural crest cells results in

A

A loss of adhesion which allows migration

89
Q

Neural crest cells differentiate into cell type depending on

A

The ECM and cell environment

90
Q

Laminin and Fibronectin

A

Cause neural crest cells to migrate