Extracellular Matrix Biology II Flashcards
Give two examples of multi-adhesive glycoproteins.
Fibronectin, Laminin
Where are Laminins found?
Basement Membrane
Describe, in full, the structure of Laminin.
It is a cross shaped molecule consisting of an alpha, beta and gamma chain
It has different parts that have different binding capabilities
The N terminus of all the chains there are globular regions
There is a coiled-coil region, which is the region in which the three chains are wrapped around each other
What causes congenital muscular dystrophy?
Absence of alpha 2 chain in laminin 2
Why is fibronectin considered essential for life?
There are no known mutations of fibronectin in humans
Describe three roles of fibronectin.
Binding to integrin and linking ECM to the actin cytoskeleton – cell binding Self-association
Binding to other ECM components
What is the general structure of fibronectin?
It is a dimer that is joined by disulphide bonds – it has various domains that can bind to different things
Describe the link between fibronectin and the intracellular compartment.
Fibronectin associated with an integrin which associates with actin – forms a mechanical continuum with the actin cytoskeleton
The fibronectin is also bound to collagen
What part of fibronectin do integrins bind to?
RGD motif
Describe the general structure of proteoglycans.
Consists of a core protein with one or more GAG chains covalently attached
What is the basic structure of GAG chains and what is a characteristic feature of GAG chains?
It is a long, unbranched chain consisting of a repeating disaccharide It has a large volume
Can form hydrated gels
What are the four families of GAG chains?
Hyaluronan
Heparan Sulfate
Chondroitin Sulfate/Dermatan sulphate
Keratan sulfate
What is unique about hyaluronan?
It doesn’t have a core protein – it is just a massive polysaccharide
It is synthesised on the cell membrane rather than by the ER
How are GAG chains linked to the core protein?
It is connected via a link tetrasaccharide
What does Decorin do?
Regulates collagen fibre size and arrangement
What does hyaline cartilage consist of?
Aggrecan aggregates – consists of aggrecan (GAG chains = keratan sulphate and chondroitin sulphate) associated with hyaluronan and a link protein
Describe how hyaline cartilage resists compressive force.
The GAG chains in aggrecan are heavily sulphated and carboxylated so it is very negatively charged
This means that it can attract osmotically active cations such as Na+ and Ca2+, which attracts water forming a gel like substance
When it experiences a compressive force, the water is squeezed out and the water returns when the compressive force is removed
What causes osteoarthritis?
Loss of extracellular matrix
What happens in fibrotic disorders?
Excess deposition of collagen – normal tissue gets replaced by collagen
