MCB Lecture 38 Connective Tissue Flashcards
What are the two structural proteins in the extracellular matrix?
Elastin
Collagen
Describe the contents of extracellular matrix
Fibrous proteins
Adhesive proteins
Ground substance: proteoglycans
What are the adhesive proteins in ECM?
Fibronectin
Laminin
What is the function of ECM? (2)
- Support
2. Regulation of cellular activities
Which cells produce ECM? (4)
Cells within the ECM, mysenchymal cells
Eg. Fibroblasts
Osteoblasts
Chondroblasts
Also epithelial cells
Describe the structure of collagen
Three alpha helices intertwine to becomes a Super helix (triple helix)
Super helices interact via cross linking to form fibrils
Fibril interact to form collagen fibres
Describe the synthesis of fibrillar collagen
- Helix translated into ER
- Three helices intertwine with disulfide bonds, propeptides present on the ends
Q3. Triple helix packaged and exocytosed - Outside the cell, the pro-peptides are cleaved, and fibrils form
- Fibres form by covalent cross links between fibrils
Where do collagen fibrils form?
Outside the cell
What are the three types of collagen?
Fibrillar
Fibrillar associated collagen
Sheet forming collagen
Describe the features of fibril associated collagen
- Flexible region where there is no helix
- Bind to fibrillar collagen
- Pro-peptides aren’t cleaved
What are propeptides?
Where are they cleaved?
What is their function?
These are peptide regions on the end of the triple helices
They are cleaved when the triple helix is exocytosed
Their function is to stop fibrils forming inside the cell. Only once the helices are outside the cells can fibrils form
How is tensile stretch in collagen regulated?
The number of cross links in the fibrils corresponds to the tensile strength
The more cross links, the stronger the fibre
What do defects in collagen cause? (4)
- Scurvy
- Ehlers Danlos syndrome
- Achondrogenesis
- Osteogenesis imperfecta
What are the features of elastin?
- Stretchy, provides elasticity
Where is elastin found?
- Arteries, especially the aorta
2. Lungs
Describe the structure of elastin
Covalently cross linked network of elastin molecules + fibrillin
What do defects in elastin cause?
- Marfan syndrome:
Problems with vasculature: vasodilation, aneurysms
Scoliosis
Dislocated lens
What causes Marfan syndrome?
Defects in fibrilhin, which is vital for elastin fibre formation
What are the general features of adhesive proteins?
- They interact with integrins in focal adhesions and hemi desmosomes
Mediate the interaction between cells and the ECM
- Multiple binding domains
What are the two forms of fibronectin?
- Soluble, present in plasma
2. Insoluble: binds to integrins
What is the sequence on fibronectin that binds to integrins?
RGD sequence
Arg, Gly, Asp
What are two defects in fibronectin?
- Fibronectin knockout: blood vessels can’t form because there is no cell migration
- Antibodies form to the RGD sequence
What is the structure of laminin?
- 3 chains: alpha, beta, gamma
The three chains are connected with disulfide bonds - Multiple binding domains
Where is laminin located?
In the basement membrane
What do laminin mutations cause? (2)
- Muscular dystrophy
2. Problems with Neuromuscular junctions
What are basement membranes?
This is the layer of proteins under the epithelial cells
Mediates the interaction between epithelial tissue and ECM
What are the functions of basement membranes?
- Growth factors
2. Modulates cell behaviour
Describe the structure of ground substance
Proteoglycans in an aqueous environment, forming a gel
Describe the structure of proteoglycans
Protein core
Linker Tetrasaccharides
Glucosaminoglycans (GAGs)
What are proteoglycan aggregates?
This is when a molecule such as Hyaluronan binds many protein cores of proteoglycans.
This creates a huge proteoglycans, comparable in size to a bacterium
What is hyaluronan?
It is a molecule to which multiple proteoglycans bind (at the protein core), forming an aggregate
What are the general features of proteoglycans? What does this mean for the composition of the ground substance?
- The sugars are negatively charged
Na+ is attracted, pulling water with it.
The osmotic pressure brings about
- Resistance to compressive forces
- Gel like characteristic
Describe how proteoglycans can inhibit and enhance ligand signalling on cells
- Bind to secreted proteins (ligands) and present them to receptors
- Bind to secreted proteins (ligands) and sequester them from receptors
- Enhance the diffusion of protein ligands
What sort of bonds are between collagen fibrils?
Covalent
What is the name of the collagen that is present in the ER?
What is its structure?
Pro collagen
It is the super helix of alpha helices, with propeptides attach
What is the handedness of collagen helices?
Left handed
Which type of bonding is present in elastin networks?
Covalent
What makes up an elastic fibre?
Elastin and fibrillin
A single collagen alpha helix is made up of…
Gly-X-Y triplets
In a collagen alpha helix, the ‘X’ and ‘Y’ correspond to…
X: proline or lysine
Y: hydroxyproline or hydroxylysine
