Strand 2 - Extracellular matrix Flashcards

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
what does the **ECM** provide support and strength via? which two structures?
cartilage and the basal lamina
26
in which 4 processes does the ECM facilitate cell migration and cell shape?
embryonic development angiogenesis wound repair tumour development
27
what 6 components make up the basal lamina?
laminin type 4 collagen type 18 collagen nidogen perlecan fibronectin
28
cells found in connective tissue are indigenous, including.....
primitive mesenchymal cells
29
which type of tissue do primitive mesenchymal cells lead to the generation of? give 2 examples of cells which contain this type of tissue
connective tissue cells such as adipocytes and mast cells
30
which molecules, found in connective tissues, synthesise most of the molecules found in the ECM?
fibroblasts
31
name two **specialised** cell types found in connective tissue
chondrocytes and osteoblasts
32
which 3 molecules make up the connective tissue ECM?
GAGs fibrous proteins (collagen) glycoproteins (elastin)
33
when connective tissue ECM becomes calcified, which structures can it form? 2 examples
bone and teeth
34
when connective tissue ECM becomes transparent, what structure can it form?
cornea
35
which 2 components make up a GAG?
sulphated disaccarides and core proteins
36
give an example of a small core protein in GAGs
decorin
37
give an example of a large core protein in GAGs
aggrecan
38
which molecule can bind up to 1000 GAG molecules? (allowing self aggregation)
hyaluronan
39
collagen is a ......... stranded helical structure
triple
40
how many alpha chains make up the helix in collagen?
3
41
what is the function of procollagen inside cells?
to prevent self aggregation
42
terminal procollagen extensions are cleaved by which enzyme?
procollagen proteinase
43
elastins make up most of the ECM in which blood vessel?
arteries
44
what do fibronectins bind in connective tissue?
intergrins or other cell membrane/matrix proteins
45
what are the key receptors that bind ECM components to the cytoskeleton, mainting strength ?
integrins
46
integrins are made up of what 4 components? ( hint: 2 chains, 2 domains)
alpha chain beta chain N terminal domain intracellular domain
47
which adaptor molecule connects integrins with the cytoskeleton (e.g actin filaments)?
talin
48
intergrins exist in which 2 conformations?
active and inactive
49
cells that migrate through the ECM use integrins to do what?
to pull themselves through the ECM
50
which kinases do integrins recruit, leading to altered gene expression (ECM homeostasis)?
Focal Adhesion Kinases / FAKs
51
the human degradome comprised of genes which encode which type of enzyme?
genes which encode proteinases
52
what are the 5 types of proteinases? (hint: start with amino acids and end in -ase)
aspartic proteinases cysteine proteinases threonine proteinases serine proteinases metallo proteinases
53
matrix metalloproteinases (MMPs) are key modifiers of what?
the ECM
54
name 2 members of the metalloproteinase family (not including MMPs) which are involved in ECM breakdown
ADAM and ADAMTS
55
what are metalloproteinases characterized by? (hint: a domain)
Zn 2+ binding domain
56
what are metalloproteinases inhibited by?
alpha-2 macroglobulins and TIMPS
57
ECM cleavage creates catabolic fragments called what? which have allowed researchers to monitor ECM breakdown in disease
neo epitopes
58
damage to the matrix induces inflammation which promotes ECM synthesis necessary for ...... repair
wound repair
59
what type of immune molecule influences both ECM synthesis and catabolism?
inflammatory cytokines
60
what are the 3 main types of cartilage?
hyaline, fibro, elastic
61
where on the body is hyaline cartilage found?
ribs nose larynx trachea articular joints
62
where is fibro cartilage found? (hint: within articular joints)
joint capsules, ligaments
63
where is elastic cartilage found? (hint: think sound and swallowing)
ear, epiglottis, larynx
64
hyaline cartilage is a precursor for what structure in the body?
bone
65
what are the 2 key components found in articular cartilage? (hint: needed for strength)
type 2 collagen and aggrecan
66
what is is Ehlers - Danlos syndrome a defect in, with regards to cartilage, and what does it result in ?
a defect in the deposition of collagen results in hyperextensible joints
67
Aggrecan complexes are highly charged due to what?
GAG content
68
the hydrated gel (due to proteoglycans being highly charged) in cartilage attracts...... which does what?
attracts water results in turgor / provides strength / provides resistance to compression
69
what do chondrocytes in **adult** **cartilage** secrete? and what are chondrocytes rich in (2 cellular structures)?
type 2 collagen and aggrecan rich in RER and golgi
70
what key transcriptional factor do chondrocytes have?
expression of sox-9
71
when does chondrocyte proliferation begin?
embryonic development
72
what 4 things does chondrocyte proliferation require?
TGF - beta FGF (fibroblast growth factor) IGF-1 (insulin like growth factor) PTHrP (parathyroid hormone related protein)
73
In endochondrial ossification what is replaced by bone during foetal developement?
"cartilage model" is replaced
74
spatial patterning of chondrocytes during bone formation is facilitated by which group of molecules?
morphogens
75
via which type of signalling do morphogens spatially pattern chondrocytes during bone formation?
via inductive signalling
76
Which members of the hedgehog family of proteins control production of the morphogen PTHrP?
SHH, DHH, IHH
77
Which two molecules interact via positive feedback loops to maintain spatial chondrocyte proliferation? (Hint: a member of the hedgehog family and a morphogen)
IHH and PTHrP
78
In drosophila, hedgehog interacts with a)........ and b)......... to keep the proteolytic processing of c)....... turned off
a) Patched b) smoothened c) Cubitus Interruptus (Ci)
79
what 2 things does osteoid ECM contain?
hydroxyapatite and collagen
80
cartilage is catabolized during the formation of bone in embryonic development. What happens next?
Cartilage becomes calcified Osteoblasts get trapped
81
Which molecule maintains chondrocyte proliferation, cartilage production and prevents their terminal differentiation?
PTHrP
82
As cells move further away from the central ossification centres in bone formation what do they recieve less of? What does this reduce?
PTHrP IHH and therefore less PTHrP, becoming more osteoblast like
83
give 2 examples of articulated joints
hip and knee
84
define osteoarthritis
slow, progressive loss of ECM
85
what is the chondrogenic phenotype of osteoarthritis?
mechanical damage without obvious cause (primary OA)
86
what does osteoarthritis result in clinically?
limited joint movement, joint deformity, inflammation, severe pain
87
in cartilage, what are microfilaments of the cytoskeleton attached to ?
integrins
88
what are integrins attached to in cartilage?
collagen fibres
89
in cartilage, which complexes are the cartilage fibres attached to?
proteogylcan complexes (polysaccaride + proteoglycan)
90
what does DMM stand for in osteoarthritis?
destabilisation of the medial meniscus
91
Does osteoarthritis depend more on collagen cleavage or aggrecan destruction?
collagen cleavage
92
give an example of a collagenase
MMP-13
93
Is osteoarthritis monogenic or polygenic?
polygenic
94
which growth factor family is GDF-5 from? what is it involved in?
growth factor member of TGF-beta family involved in ECM homeostasis
95
Where is RUNX2 located on chromosomes and what is it a transcription factor for?
6p 21.1 txn factor for endochondrial ossification - MMP-13
96
Where is PTHLH located on the chromosomes? What does it encode?
12p 11.22 PTHrP
97
SMAD3 is an intracellular signalling protein involved in ....... secretion and reducing the secretion of the collegenase called.....
TGF beta MMP-13
98
what is MMP-13 inhibited by?
TIMP-3
99
name two current therapies for osteoarthritis
surgery and NSAIDs
100
Rheumatoid arthritis is the progressive loss of the ECM in articular cartilage due to what?
immune cell mediated damage (rheumatoid arthritis is an autoimmune disease)
101
rheumatoid factor, found in the blood of many patients, is classed as an auto.....
auto antibody
102
rheumatoid is an IgM that bind which other Ig?
IgG
103
rheumatoid arthritis patients have nuclear antigen molecules react with epitopes that contain.......... amino acids
citrullinated amino acids
104
what is a citrullinated amino acid?
arginine becomes a citrulline
105
is rhemuatoid factor found in the blood of people who DON'T have rheumatoid arthritis?
yes
106
some epithelial cancers have been known to downregulate which type of cadherin?
E