Tissues 4 (ECM) Flashcards
What is a laminin?
Ubiquitous basement membrane protein
Wha is the structure of Laminin?
- cross shaped molecule consisting of an alpha, beta and gamma chain
- different parts that have different binding capabilities
Why is fibronectin considered essential for life?
There are no known mutations of fibronectin in humans
What are the 3 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?
- dimer (2 units) joined by disulphide bonds
- has various domains that can bind to different things
What is the link between fibronectin and the intracellular compartment?
- fibronectin associated with an integrin which associates with actin
– forms mechanical continuum with actin cytoskeleton - fibronectin bound to collagen
What part of fibronectin do integrins bind to?
RGD motif
What is 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?
- long, unbranched chain consisting of a repeating disaccharide
- 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?
- doesn’t have a core protein (just a massive polysaccharide)
- 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?
- binds to collagen fibres
- regulates fibrillogenesis (collagen fibre size & arrangement)
What does hyaline cartilage consist of?
- core protein (aggrecan) linked to hyaluronan with link protein (aggregates)
- aggrecan GAG chains = keratan sulphate and chondroitin sulphate
How does hyaline cartilage resists compressive force?
- GAG chains in aggrecan heavily sulphated & carboxylated so very negatively charged
- attracts osmotically active cations (Na+ & Ca2+) which attract water forming a gel like substance
- with compressive force, water squeezed out and returns when force is removed
What causes osteoarthritis?
- loss of extracellular matrix
- cartilage that cushions joint compression is lost
What happens in fibrotic disorders?
Too much ECM - normal tissue gets replaced by collagen
What is a modular architecture of glycoproteins?
Composed of protein domains of 50-200 amino acids
What do all 3 laminin chains have in common?
A globular region at the N terminus
What is the coiled region of a laminin?
the region in which the three chains are wrapped around each other
What does multi-adhesive mean in terms of glycoproteins?
Multifunctional as different regions can bind to different molecules
What are the features of fibronectin?
- large
- multi-adhesive
- derived from one gene
- exists in insoluble fibrillation matrix or soluble plasma protein
What are the functions of fibronectin?
- regulates cell adhesion & migration in embryogenesis & tissue repair
- promotes blood clotting
What is decorin?
- single GAG chain attached
- dermatan sulfate chain
What happens to aggrecan in osteoarthritis?
- degrades (cleaved by aggrecanases & metalloproteinases)
- fragments lost in synovial fluid
What happens in fibrosis?
Scar tissue replaces normal tissue
