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BMS2002 Cell Biology and Disease > Strand 2 - Extracellular matrix > Flashcards

Strand 2 - Extracellular matrix Flashcards

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1
Q

which 3 cell tissue types have a high frequency of cell-cell contact but a low frequency of cell- ECM contact?

A

epithelial, muscular, nervous

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2
Q

which cell tissue type has a low frequency of cell-cell contact but a high frequency of cell- ECM contact?

A

connective tissue

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3
Q

how are mechanical forces transmitted from cell to cell in epithelial tissue?

A

via cytoskeletal filaments (also give strength)

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4
Q

in epithelial tissue, what are the individual cells linked by?

A

cell junctions

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5
Q

cells in epithelial tissue are asymmetrical or symmetrical?

A

asymmetrical

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6
Q

cells in epithelial tissues are polarized or non polarized?

A

polarized

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7
Q

epithelial cells are attached to a thin layer of connective tissue comprising mostly of ECM called the……?

A

basal lamina

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8
Q

the 4 shapes of epithelial cells are…… (hint: CCSS)

A

columnar
cuboidal
squamos
stratified

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9
Q

What are the 4 types of cell junctions found in epithelial cells?

A

adherens junctions
desmosomes
tight junctions
gap junctions

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10
Q

what do adherens junctions hold onto each other via?

A

cadherin molecules

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11
Q

which 3 subfamilies of cadherins are there?

A

E, N and P cadherin

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12
Q

is cadherin binding homo or heterophillic?

A

homophillic - they bind to themselves

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13
Q

Which region of cadherin molecules does Ca2+ bind to?

A

(flexible) hinge region

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14
Q

what does the binding of Ca2+ prevent on cadherins?

A

flexing of the hinge regions (promotes homophillic binding of Ca 2+)

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15
Q

which domain does actin interact with on cadherins??

A

the intracellular domain

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16
Q

how does actin interact with the intracellular domain of cadherins? which two molecules?

A

via catenins and vinculin

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17
Q

give 3 examples of catenins

A

alpha catenin
beta catenin
p120 catenin

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18
Q

give an example of an adaptor protein that interacts with actin/domain of cadherins

A

vinculin

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19
Q

desmosomes contain specialised cadherins that connect with ……. rather than actin filaments (adherens junctions)?

A

intermediate filaments

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20
Q

tight junctions in epithelial cells act as what?

A

a selective permeability barrier

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21
Q

name a differential transporter molecule, expressed on the apical and basal plasma membranes, found in the small intestine

A

glucose (GLUT) transporters

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22
Q

name 2 tight junction proteins

A

claudin and occludin

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23
Q

gap junctions in epithelial cells are channels/pores made from which 2 molecules?

A

connexins and innexins

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24
Q

what do gap junctions allow to pass through their pores?

A

intracellular/water soluble molecules

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25
Q

what does the ECM provide support and strength via? which two structures?

A

cartilage and the basal lamina

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26
Q

in which 4 processes does the ECM facilitate cell migration and cell shape?

A

embryonic development
angiogenesis
wound repair
tumour development

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27
Q

what 6 components make up the basal lamina?

A

laminin
type 4 collagen
type 18 collagen
nidogen
perlecan
fibronectin

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28
Q

cells found in connective tissue are indigenous, including…..

A

primitive mesenchymal cells

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29
Q

which type of tissue do primitive mesenchymal cells lead to the generation of? give 2 examples of cells which contain this type of tissue

A

connective tissue

cells such as adipocytes and mast cells

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30
Q

which molecules, found in connective tissues, synthesise most of the molecules found in the ECM?

A

fibroblasts

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31
Q

name two specialised cell types found in connective tissue

A

chondrocytes and osteoblasts

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32
Q

which 3 molecules make up the connective tissue ECM?

A

GAGs
fibrous proteins (collagen)
glycoproteins (elastin)

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33
Q

when connective tissue ECM becomes calcified, which structures can it form? 2 examples

A

bone and teeth

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34
Q

when connective tissue ECM becomes transparent, what structure can it form?

A

cornea

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35
Q

which 2 components make up a GAG?

A

sulphated disaccarides and core proteins

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36
Q

give an example of a small core protein in GAGs

A

decorin

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37
Q

give an example of a large core protein in GAGs

A

aggrecan

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38
Q

which molecule can bind up to 1000 GAG molecules? (allowing self aggregation)

A

hyaluronan

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39
Q

collagen is a ……… stranded helical structure

A

triple

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40
Q

how many alpha chains make up the helix in collagen?

A

3

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41
Q

what is the function of procollagen inside cells?

A

to prevent self aggregation

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42
Q

terminal procollagen extensions are cleaved by which enzyme?

A

procollagen proteinase

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43
Q

elastins make up most of the ECM in which blood vessel?

A

arteries

44
Q

what do fibronectins bind in connective tissue?

A

intergrins

or other cell membrane/matrix proteins

45
Q

what are the key receptors that bind ECM components to the cytoskeleton, mainting strength ?

A

integrins

46
Q

integrins are made up of what 4 components?
( hint: 2 chains, 2 domains)

A

alpha chain
beta chain
N terminal domain
intracellular domain

47
Q

which adaptor molecule connects integrins with the cytoskeleton (e.g actin filaments)?

A

talin

48
Q

intergrins exist in which 2 conformations?

A

active and inactive

49
Q

cells that migrate through the ECM use integrins to do what?

A

to pull themselves through the ECM

50
Q

which kinases do integrins recruit, leading to altered gene expression (ECM homeostasis)?

A

Focal Adhesion Kinases / FAKs

51
Q

the human degradome comprised of genes which encode which type of enzyme?

A

genes which encode proteinases

52
Q

what are the 5 types of proteinases? (hint: start with amino acids and end in -ase)

A

aspartic proteinases
cysteine proteinases
threonine proteinases
serine proteinases
metallo proteinases

53
Q

matrix metalloproteinases (MMPs) are key modifiers of what?

A

the ECM

54
Q

name 2 members of the metalloproteinase family (not including MMPs) which are involved in ECM breakdown

A

ADAM and ADAMTS

55
Q

what are metalloproteinases characterized by? (hint: a domain)

A

Zn 2+ binding domain

56
Q

what are metalloproteinases inhibited by?

A

alpha-2 macroglobulins and TIMPS

57
Q

ECM cleavage creates catabolic fragments called what? which have allowed researchers to monitor ECM breakdown in disease

A

neo epitopes

58
Q

damage to the matrix induces inflammation which promotes ECM synthesis necessary for …… repair

A

wound repair

59
Q

what type of immune molecule influences both ECM synthesis and catabolism?

A

inflammatory cytokines

60
Q

what are the 3 main types of cartilage?

A

hyaline, fibro, elastic

61
Q

where on the body is hyaline cartilage found?

A

ribs
nose
larynx
trachea
articular joints

62
Q

where is fibro cartilage found? (hint: within articular joints)

A

joint capsules, ligaments

63
Q

where is elastic cartilage found? (hint: think sound and swallowing)

A

ear, epiglottis, larynx

64
Q

hyaline cartilage is a precursor for what structure in the body?

A

bone

65
Q

what are the 2 key components found in articular cartilage? (hint: needed for strength)

A

type 2 collagen and aggrecan

66
Q

what is is Ehlers - Danlos syndrome a defect in, with regards to cartilage, and what does it result in ?

A

a defect in the deposition of collagen

results in hyperextensible joints

67
Q

Aggrecan complexes are highly charged due to what?

A

GAG content

68
Q

the hydrated gel (due to proteoglycans being highly charged) in cartilage attracts…… which does what?

A

attracts water

results in turgor / provides strength / provides resistance to compression

69
Q

what do chondrocytes in adult cartilage secrete?

and what are chondrocytes rich in (2 cellular structures)?

A

type 2 collagen and aggrecan

rich in RER and golgi

70
Q

what key transcriptional factor do chondrocytes have?

A

expression of sox-9

71
Q

when does chondrocyte proliferation begin?

A

embryonic development

72
Q

what 4 things does chondrocyte proliferation require?

A

TGF - beta

FGF (fibroblast growth factor)

IGF-1 (insulin like growth factor)

PTHrP (parathyroid hormone related protein)

73
Q

In endochondrial ossification what is replaced by bone during foetal developement?

A

“cartilage model” is replaced

74
Q

spatial patterning of chondrocytes during bone formation is facilitated by which group of molecules?

A

morphogens

75
Q

via which type of signalling do morphogens spatially pattern chondrocytes during bone formation?

A

via inductive signalling

76
Q

Which members of the hedgehog family of proteins control production of the morphogen PTHrP?

A

SHH, DHH, IHH

77
Q

Which two molecules interact via positive feedback loops to maintain spatial chondrocyte proliferation?

(Hint: a member of the hedgehog family and a morphogen)

A

IHH and PTHrP

78
Q

In drosophila, hedgehog interacts with a)…….. and b)……… to keep the proteolytic processing of c)……. turned off

A

a) Patched
b) smoothened
c) Cubitus Interruptus (Ci)

79
Q

what 2 things does osteoid ECM contain?

A

hydroxyapatite and collagen

80
Q

cartilage is catabolized during the formation of bone in embryonic development. What happens next?

A

Cartilage becomes calcified

Osteoblasts get trapped

81
Q

Which molecule maintains chondrocyte proliferation, cartilage production and prevents their terminal differentiation?

A

PTHrP

82
Q

As cells move further away from the central ossification centres in bone formation what do they recieve less of?

What does this reduce?

A

PTHrP

IHH and therefore less PTHrP, becoming more osteoblast like

83
Q

give 2 examples of articulated joints

A

hip and knee

84
Q

define osteoarthritis

A

slow, progressive loss of ECM

85
Q

what is the chondrogenic phenotype of osteoarthritis?

A

mechanical damage without obvious cause (primary OA)

86
Q

what does osteoarthritis result in clinically?

A

limited joint movement, joint deformity, inflammation, severe pain

87
Q

in cartilage, what are microfilaments of the cytoskeleton attached to ?

A

integrins

88
Q

what are integrins attached to in cartilage?

A

collagen fibres

89
Q

in cartilage, which complexes are the cartilage fibres attached to?

A

proteogylcan complexes (polysaccaride + proteoglycan)

90
Q

what does DMM stand for in osteoarthritis?

A

destabilisation of the medial meniscus

91
Q

Does osteoarthritis depend more on collagen cleavage or aggrecan destruction?

A

collagen cleavage

92
Q

give an example of a collagenase

A

MMP-13

93
Q

Is osteoarthritis monogenic or polygenic?

A

polygenic

94
Q

which growth factor family is GDF-5 from? what is it involved in?

A

growth factor member of TGF-beta family

involved in ECM homeostasis

95
Q

Where is RUNX2 located on chromosomes and what is it a transcription factor for?

A

6p 21.1

txn factor for endochondrial ossification - MMP-13

96
Q

Where is PTHLH located on the chromosomes? What does it encode?

A

12p 11.22

PTHrP

97
Q

SMAD3 is an intracellular signalling protein involved in ……. secretion and reducing the secretion of the collegenase called…..

A

TGF beta

MMP-13

98
Q

what is MMP-13 inhibited by?

A

TIMP-3

99
Q

name two current therapies for osteoarthritis

A

surgery and NSAIDs

100
Q

Rheumatoid arthritis is the progressive loss of the ECM in articular cartilage due to what?

A

immune cell mediated damage (rheumatoid arthritis is an autoimmune disease)

101
Q

rheumatoid factor, found in the blood of many patients, is classed as an auto…..

A

auto antibody

102
Q

rheumatoid is an IgM that bind which other Ig?

A

IgG

103
Q

rheumatoid arthritis patients have nuclear antigen molecules react with epitopes that contain………. amino acids

A

citrullinated amino acids

104
Q

what is a citrullinated amino acid?

A

arginine becomes a citrulline

105
Q

is rhemuatoid factor found in the blood of people who DON’T have rheumatoid arthritis?

A

yes

106
Q

some epithelial cancers have been known to downregulate which type of cadherin?

A

E

BMS2002 Cell Biology and Disease (6 decks)

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