Lecture 12 - Other Roles Of Proteoglycans Flashcards

1
Q

What do proteoglycans allow?

A

They are adhesion molecules and allow cells to differentiate between self and non-self

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2
Q

In what organisms are cell surface proteoglycans used?

A

In simpler organisms

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3
Q

What are metazoans (sponges)?

A

They are the simplest multicellular organism and there are 3 types

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4
Q

What are the 3 types of metazoans?

A

Microciona prolifera, Halichondria Panicea and cliona celata

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5
Q

What is interesting about metazonas?

A

They can recognise their brother and sister cells even when reformed - don’t form hybrids

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6
Q

What happens if you remove the cell surface proteoglycans from the metazoans?

A

It abolish the effect of recognising brother or sister cells

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7
Q

What are the removable proteoglycans called to abolish the effect on metazoans?

A

Glyconectins

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8
Q

What do proteoglycans appear to act as?

A

Like enzymes, there is evidence that they are able to act as a receptor like protein tyrosine phosphatase

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9
Q

What is 6B4 proteoglycan?

A

It is a major soluble CS-PG in the brain and can be removed by PBS (phosphate buffer saline) and is then solubilised

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10
Q

What are two types of neurons that are examined from the cerebral cortex and the thalamus when looking at 6B4 proteoglycan (phosphocan)?

A

Cortical and thalamic neurones

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11
Q

Does 6B4 proteoglycan have anything to do with cell adhesion?

A

Coated a well with poly-l-lysine which cells cells adhere. Put in islands of 6B4 and the cells stuck to the plates with no 6B4 but with 6B4 no cells attached even with poly-l-lysine

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12
Q

6B4 is a ……

A

Anti adhesion molecule

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13
Q

What is neuritis extension?

A

Neurone throwing out protections - starting to form neurones

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14
Q

What type of neurone shows neurite extension?

A

Cortical neurones not thalamic

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15
Q

What is the structure like of 6B4 chain?

A

It has an N and C terminal, N terminal seems to be like carbonic anhydrase. At the C terminal there are chondroite sulphates found.

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16
Q

What does it mean if Cs chains are attached?

A

That the composition is glycine and serine rich

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17
Q

Why is serine important?

A

As it has an OG group that the GAG chain attaches to

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18
Q

What is glycine important?

A

Because it is small so it allows for a lot of packing of the GAG chains

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19
Q

What is chondroitinase ABC?

A

An enzyme that chews off the chondroitin sulphate chains - it has no effect on neurite extension

20
Q

What can abolish neurite extension?

A

If an antibody attaches to the N terminal where the carbonic anhydrase like region is - it abolishes the neurite extension

21
Q

What does chondroitinase digestion abolish?

A

The repulsive effects, the C terminal is the repulsive effect

22
Q

The more 6B4 proteoglycan = the more

A

Neurite extension - it is concentration dependent of 6B4

23
Q

What does 6B4 modulate?

A

It modulates morphogenesis and differentiates neurones depending on its spatiotemporal distribution and the cell type in the brain

24
Q

What is found under the N terminal (carbonic anhydrase like region)? Of phosphocan

A

A fibronectin like repeat

25
Q

What is found on the C terminal of phosphocan?

A

Tyrosine phosphatase

26
Q

What is the invading organism in malaria? - the role of proteoglycans in binding invading pathogens

A

Circumsporozoites - most common one in malaria is plasmodium

27
Q

What does the pathogen (circumsporozoites Enter)?

A

It enters the hepatocytes in the liver within minutes of feeding by infected mosquitos

28
Q

What does the pathogen bind to?

A

It binds to syndecan on the heparan sulphate (HS) proteoglycan on the cell surface

29
Q

What treatments prevent the binding and stop the sporozoite from entering the cell?

A

Tyrosine and heparitinases

30
Q

What is the interaction like between the sporozoite and the HS chains?

A

It is a charge:charge one

31
Q

What does the surface protein on the sporozoite contain?

A

It contains lots of basic amino acids in clusters e.g. lysine and arginine which interact with the negative charges on the HS GAG chains

32
Q

Different surface proteoglycans are recognised by ….

A

Different pathogens

33
Q

What is syndecan?

A

It is a cell surface proteoglycan which has an extracellular domain

34
Q

What does the extracellular domain of syndecan have?

A

It has heparan sulphate domains (3 of them) called the ecto-domain

35
Q

What amino acid is close to the cell membrane transmembrane domain in syndecan?

A

222-226

36
Q

What can syndecan act as?

A

It can act as a receptor as it has its tyrosine residues phosphorylated inside and get signalling by phosphorylation

37
Q

What can proteoglycans act as?

A

Receptors

38
Q

What was used for syndecan methods?

A

Site directed mutagenesis, mutate the amino acids 222-226 through an invasion assay

39
Q

Does mutation alter binding to collagen?

A

Hasn’t effected the cells to interact with collagen but is has affected the ability of them to stay attached

40
Q

What does the core protein of syndecan-1 have?

A

It has anti invasion properties

41
Q

What are aggrecans in the brain called?

A

Lecticans - any proteoglycan with a G1 and G3 (lectin domain)

42
Q

What are some examples of major proteoglcyans in the brain?

A

Versican, aggrecan, neurocan and brevican

43
Q

What does versican interact with?

A

It interacts strongly with Tenascin R a brain matrix protein

44
Q

What does Tenasxin R exist as?

A

Monomer, dimmer and trimer interacting with versican in glial tissue as part of white matter

45
Q

What does the brain need?

A

The brain needs a buffer against pressure changes

46
Q

What does the mutation of 222-226 AVAAV not affect?

A

Collagen binding and cell spreading