Tissues 4 Flashcards
Name 1 glycoprotein structure found everywhere in basal laminae.
Laminins (very large and multi-adhesive)
What are the 3 chains present in laminas?
Alpha, beta, gamma chains
Which cell surface receptors can laminins interact with?
Integrins
Dystroglycans
(amongst others)
Name some components of the basal lamina that Laminin can interact with.
- Type 4 collagen
- Nidogen
- Proteoglycans
What are chain mutations in laminin associated with?
- Muscular dystrophy
2. Epidermolysis Bullosa
What does the absence of the a2-chain in laminin 2(11) cause?
Congenital muscular dystrophy , presenting with hypotonia. general weakness and joint deformities.
What are fibronectins?
Glycoproteins
Present as either insoluble fibrillar network or soluble plasma protein.
Where are fibronectins found?
In body fluid or in ECM
How many genes derive fibronectin?
1 gene.
Variations in fibronectin arise from splicing the 1 gene.
Fibronectins are multi -…… and form …….?
Multiadhesive, form dimers,
Why are there no known variations of the fibronectin genes?
Functional fibronectin is crucial for viability.
How does fibronectin form a mechanical continuum with the actin cytoskeleton?
By binding with integrin on cell surface.
Integrin is transmembranous and associated with actin cytoskeleton
What is an RGD motif?
Sequence of aas.
Arg-Gly-Asp
What type of fibronectin produces an RGD motif recognised by integrin?
Type III Fibronectin
What is a proteoglycan?
Heavily glycosylated proteins.
Core protein associated with one or more Gycosaminoglycan chains (GAG) chains covalently attached.
What are GAG chains?
- Long, unbranched chains
- REPEATING DISACCHARIDES
- Huge volume relative to mass
- Hydrated gels resistant to compression
Which proteoglycan family is found in the basement membrane?
Perlecan
What proteoglycan family is involved in aggregating and is involved with hyaluronan?
Aggrecan
Decorin?
Small, leucine rich proteoglycan family
Cell surface proteoglycan family?
Syndecans 1-4
In GAG chains, 1 out of 2 repeating sugars is always an amino sugar. T or F?
T.
How do the proteoglycans attract water and become gels?
They are carboxylated and sulphated - and are highly negatively charged.
What are the 4 main GAG chain groups?
- Hyaluronan
- Chondroitin sulfate and dermatan sulphate
- Heparan sulphate
- Keratan sulphate
Hyaluronan. Describe.
- aka hyaluronic acid
- is simply a carbohydrate chain - no core protein
- synthesised at the cell surface, not ER or Golgi
- NOT SULPHATED
- HUGE - 1 molecule can have same volume as bacterium
- Consists of upto 25000 repeated disaccharides
- GAG and core protein linked by serine residue in core protein which binds to a link tetrasaccharide in GAG molecule
Dermatan Sulphate structure. Describe.
Repeating disaccharides = iduronic acid and N-acetylgalactosamine-4-sulphate
Chondroitin sulphate structure.
Repeating structures = glucuronic acid and N-acetylgalactosamine-4-sulphate
Describe decorin.
Small proteoglycan that binds to collagen fibres and is essential for collagen fibre formation.
Lack of decor may result in fragile skin with reduced tensile strength.
Has only one dermatan sulphate molecule as a GAG side chain.
Describe cartilage.
Network of proteoglycans with Type 2 collagen interwoven to form fibrils.
Describe aggrecan.
- Major cartilage matrix constituent.
- Core protein with Chondroitin sulphate GAG chains on the end of the protein.
- Keratan sulphate GAG next to CS
- Hyaluronan next to keratan sulphate.
- Link protein binds hyaluronan to binding region.
What does aggrecan form?
Supramolecular complexes.
Describe how osteoporosis arises.
- Aggrecan GAGs highly sulphated, lots of carboxyl groups.
- Therefore, Multiple negative charges on aggrecan molecule.
- Therefore, cations attracted (e.g. Na), which are osmotically active.
- Lots of water retained, forming a gel.
- Water allows resistance to compressive forces.
- Osteoarthritis = excess loss of ECM. Painful and stiff joints and loss of gel.
What degrades aggrecan?
Aggrecanase and metalloproteinases.
What is liver cirrhosis?
- Fibrotic disorder
2. Excessive production of fibrous connective tissue in liver.
