Lecture 12 - Other Roles Of Proteoglycans Flashcards
What do proteoglycans allow?
They are adhesion molecules and allow cells to differentiate between self and non-self
In what organisms are cell surface proteoglycans used?
In simpler organisms
What are metazoans (sponges)?
They are the simplest multicellular organism and there are 3 types
What are the 3 types of metazoans?
Microciona prolifera, Halichondria Panicea and cliona celata
What is interesting about metazonas?
They can recognise their brother and sister cells even when reformed - don’t form hybrids
What happens if you remove the cell surface proteoglycans from the metazoans?
It abolish the effect of recognising brother or sister cells
What are the removable proteoglycans called to abolish the effect on metazoans?
Glyconectins
What do proteoglycans appear to act as?
Like enzymes, there is evidence that they are able to act as a receptor like protein tyrosine phosphatase
What is 6B4 proteoglycan?
It is a major soluble CS-PG in the brain and can be removed by PBS (phosphate buffer saline) and is then solubilised
What are two types of neurons that are examined from the cerebral cortex and the thalamus when looking at 6B4 proteoglycan (phosphocan)?
Cortical and thalamic neurones
Does 6B4 proteoglycan have anything to do with cell adhesion?
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
6B4 is a ……
Anti adhesion molecule
What is neuritis extension?
Neurone throwing out protections - starting to form neurones
What type of neurone shows neurite extension?
Cortical neurones not thalamic
What is the structure like of 6B4 chain?
It has an N and C terminal, N terminal seems to be like carbonic anhydrase. At the C terminal there are chondroite sulphates found.
What does it mean if Cs chains are attached?
That the composition is glycine and serine rich
Why is serine important?
As it has an OG group that the GAG chain attaches to
What is glycine important?
Because it is small so it allows for a lot of packing of the GAG chains
What is chondroitinase ABC?
An enzyme that chews off the chondroitin sulphate chains - it has no effect on neurite extension
What can abolish neurite extension?
If an antibody attaches to the N terminal where the carbonic anhydrase like region is - it abolishes the neurite extension
What does chondroitinase digestion abolish?
The repulsive effects, the C terminal is the repulsive effect
The more 6B4 proteoglycan = the more
Neurite extension - it is concentration dependent of 6B4
What does 6B4 modulate?
It modulates morphogenesis and differentiates neurones depending on its spatiotemporal distribution and the cell type in the brain
What is found under the N terminal (carbonic anhydrase like region)? Of phosphocan
A fibronectin like repeat
What is found on the C terminal of phosphocan?
Tyrosine phosphatase
What is the invading organism in malaria? - the role of proteoglycans in binding invading pathogens
Circumsporozoites - most common one in malaria is plasmodium
What does the pathogen (circumsporozoites Enter)?
It enters the hepatocytes in the liver within minutes of feeding by infected mosquitos
What does the pathogen bind to?
It binds to syndecan on the heparan sulphate (HS) proteoglycan on the cell surface
What treatments prevent the binding and stop the sporozoite from entering the cell?
Tyrosine and heparitinases
What is the interaction like between the sporozoite and the HS chains?
It is a charge:charge one
What does the surface protein on the sporozoite contain?
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
Different surface proteoglycans are recognised by ….
Different pathogens
What is syndecan?
It is a cell surface proteoglycan which has an extracellular domain
What does the extracellular domain of syndecan have?
It has heparan sulphate domains (3 of them) called the ecto-domain
What amino acid is close to the cell membrane transmembrane domain in syndecan?
222-226
What can syndecan act as?
It can act as a receptor as it has its tyrosine residues phosphorylated inside and get signalling by phosphorylation
What can proteoglycans act as?
Receptors
What was used for syndecan methods?
Site directed mutagenesis, mutate the amino acids 222-226 through an invasion assay
Does mutation alter binding to collagen?
Hasn’t effected the cells to interact with collagen but is has affected the ability of them to stay attached
What does the core protein of syndecan-1 have?
It has anti invasion properties
What are aggrecans in the brain called?
Lecticans - any proteoglycan with a G1 and G3 (lectin domain)
What are some examples of major proteoglcyans in the brain?
Versican, aggrecan, neurocan and brevican
What does versican interact with?
It interacts strongly with Tenascin R a brain matrix protein
What does Tenasxin R exist as?
Monomer, dimmer and trimer interacting with versican in glial tissue as part of white matter
What does the brain need?
The brain needs a buffer against pressure changes
What does the mutation of 222-226 AVAAV not affect?
Collagen binding and cell spreading
