Extracellular Matrix Biology II Flashcards
What are Laminins?
They are ubiquitous basement membrane glycoproteins Contains of 3 chains - one each of an a, b and g chain Forms a CROSS-SHAPED MOLECULE Very LARGE Multi-adhesive Derived from several genes Interact with cell surface receptors Found in ALL basement membranes
Mutations associated with inherited disease e.g. muscular dystrophy and epidermolysis bullosa.
Laminin Structure?
At the N terminus all the chains have Globular Regions.
Coiled-Coil Domain - where the three chains are wrapped around each other.
Different regions on the laminin have different binding capacities.
Which disease is caused by Absence of a2 in laminin 2
Congenital Muscular Dystrophy
Hypotonia
Generalised weakness
Deformities of the joints
What is Fibronectin?
NOT found in basal membranes but is a major connective tissue glycoprotein. Exists as both insoluble fibrillar matrix or soluble plasma protein
Multi-Adhesive + Large + Important in regulating cell adhesion and migration in embryogenesis and tissue repair. Important for wound healing
no known mutations - suggests its essential for life.
Fibronectin Structure?
Dimer
Two units are linked by a disulphide bridge
linked to the actin cytoskeleton via integrins
Integrin binds to fibronectin via RGD molecules
Integrin binds to the RGD sequence which is on the cell binding site.
What are Proteoglycans?
Consists of a CORE PROTEIN onto which one or more GLYCOSAMINOGLYCAN (GAG) CHAINS are covalently attached.
What are GAGs
GAG chains are long, unbranched sugars consisting of a REPEATING DISACCHARIDE - occupies a large volume compared to the mass.
They form hydrated gels which can resist compression.
Proteoglycan families?
Basement Membrane e.g. perlecan
Aggregating (interact with hyaluron) e.g. aggrecan
Small Leucine-Rich e.g. decorin
Cell Surface e.g. syndecans 1-4
Describe GAG chains?
One of the two sugars in the repeating disaccharide is always an amino sugar.
Highly Negatively Charged - many GAGs are sulfated or carboxylated
Four main groups of GAG chains: Hyaluron Chondroitin Sulfate/Dermatan Sulfate Heparan Sulfate Keratan Sulfate
Describe Hyaluron
UNIQUE - NO CORE PROTEIN - it only has a carbohydrate chain
Synthesised in the cell surface - NOT in the ER/Golgi
Unsulfated
A single long chain has up to 25,000 repeat disaccharides
Describe Decorin?
Small proteoglycan
Binds to collagen fibres
Mice who cannot make decorin have fragile skin and reduced tensile strength
Regulates collagen fibre size and arrangement
What is Hyaline Cartilage?
Most abundant type of cartilage
Rich in AGGRECAN
Cushions the ends of long bones
Aggrecan is responsible for this cushioning effect
What is Aggrecan?
The core protein of aggrecan is linked to hyaluronan
Together this makes a complex and it has a link protein which makes the structure very LARGE
Aggrecan Aggregates - the complex of aggrecan, hyaluronan and the link protein
How does Aggrecan Function with Cartilage?
GAGs of aggrecan are highly sulfated many carboxyl groups = HIGHLY NEGATIVELY CHARGED
attracts cations that are osmotically active
large amount of WATER is retained
It forms a gel - if you put pressure on the structure, the water gets squeezed out and if the compressive load is removed - the water returns.
What is Osteoarthritis?
There is loss of extracellular matrix, and cartilage, but inflammation and new bone formation.
This can lead to joint stiffness and the rubbing of bone against bone.
