Extracellular Matrix Flashcards
What are the 5 types of molecules found within ECM?
Fibrins -Elastin, Collagen,
Ground Substances- Proteoglycans, Glycosaminoglycans (typically hyaluronan), Glycoproteins
How many types of collagen are there?
28
What are the structural components of collagen?
3 collagen polypeptides secreted into ECM form triple helix
Formed of triple amino acid repeat (Glycine -X -Y)
Where is collagen type 1 found?
Skin, in tendons, and ligaments, and bone, fibrocartilage
Where is collagen type 2 found?
Hyaline cartilage
Where is collagen type 3 found?
Found in tissue, liver, lymphoid organs, granulation tissue (i.e. reticulin)
Where is collagen type 4 found?
Basement membrane
Where is collagen type 5 found?
Linker to basement membrane, and associates with collagen 1 in cornea
What is the purpose of elastin?
Enables shape recovery following deformation,
What is another name for collagen 3?
Reticulin
How is elastin assembled
Fibrous, assembly relies on presence of glycoprotein fibrillin which gets incorporated into the elastin fibre.
Where is elastin found?
In tissue (lungs, bladder and blood vessels)
What staining would you use when looking for elastin or collagen?
Van Gieson Stain
It would stain dark pink/purple and help differentiate between smooth muscle and
What are proteoglycan functions?
Highly negatively charged, therefore attracts water.
This retention supplies resistance to forces and hydration
What are Glycosaminoglycans (GAGs)and what do they form?
Chains of repeating disaccharide units.
Form carbohydrate part of proteoglycans
What Glycosaminoglycans (GAGs) are used in forming cartilage?
Chondroitin Sulphate
Keratan Sulphate
What glycosaminoglycans (GAGs) form synovial fluid?
Hyaluronan (hyaluronic acid)- also found in other body tissues
Can bind 10,000 times its own weight.
What glycosaminoglycans (GAGs) form basement membrane?
Heparan Sulphate
What are proteoglycans?
Assembly of GAGs along a protein core (95% carbohydrate)
What is the location and the GAGs that form Aggrecan?
Cartilage
Keratan Sulphates
Chondroitin Sulphates
What is the location and the GAGs that form Perlecan?
Basement Membrane
Heparan Sulphate
What is the location and the GAGs that form Syndecan?
Cartilage
Chondroitin Sulphate
Heparan Sulphate
What is the location and the GAGs that form Decorin?
Widespread in connective tissue
Chondroitin Sulphate
Dermatan Sulphate
What are the components of Aggrecan and its primary role in the body?
Assemble along Hyaluronan Core to form large negatively charged aggregate
In cartilage and joints, it interacts strongly with Collagen T2, to help resist deformation
What are different types of glycoproteins involved with the ECM?
Fibrillin
Fibronectin
Laminin
What is the functions of Fibrillin?
Controls deposition and orientation of elastin
What is the function of Fibronectin?
Link basement membrane
Cell attachment to basement membrane
Organize ECM
What is the function of Laminin?
Organize basement membrane
Interacts with the integrins (alpha-4, beta-4) found in hemidesmosomes, helping to attach cells to the basement membranes (i.e. dermal-epidermal junction, hemidesmosomes bind to laminins)
What is a glycoprotein composed of?
Protein and carbohydrate chains.
i.e. Oligosaccharide chain with amino acid side- chains covalently linked to it
What cell is largely responsible for the production of ECM?
Fibroblasts
Synthesize & secreted by fibroblast as fibrous proteins which undergo post-translational modifications, and are then assembled
What are the fibrous proteins, posttranslational modifications, and proteins assembly of collagen?
Procollagen -> glycosylation and hydroxylation -> triple helix
What are the fibrous proteins, posttranslational modifications, and proteins involved in the formation of elastin?
Tropoelastin -> hydroxylation -> fibrillin scaffolding, cross-linked fibres
How can the ECM be targetted by invading pathogens?
Clostridium species and bacillus cereus secrete collagenases that break down ECM and aid in their invasion
What role does ECM play in relation to tumour cells?
Tumour cells can secrete and recruit other cells that secrete Matrix Metalloproteases that can break down the ECM, aiding in invasion of tumour cells
Supravalvular- Aortic Stenosis is a condition relating to ECM. Explain its cause and impact.
Caused autosomal dominant inheritance resulting in mutation of elastin, causing aortic valve defects (aorta needs lots of elastin).
This causes restrictions in blood flow and can be fatal
Marfan Syndrome is a condition of the ECM. Explain its cause and impact.
Mutations in fibrillin-1 gene (needed for organization of elastin fibre), so mutations will impact structures dependent on fibrillin, causing reduction in elastin.
Causes skeletal, ocular, & cardiovascular abnormalities
Alport syndrome is a condition of the ECM. Explain its cause and impact.
Hereditary kidney disease
Mutations in collagen 4 gene causes defect in type 4 collagen.
Structural abnormalities of glomerular basement membrane (and in eye and ear).
Dysfunction leads to proteinuria and haematuria (protein and blood in urine)
Ehlers-Danlos syndrome is a condition of the ECM. Explain its cause and impact.
Collagen 1, 3, 5 mutations
Impacts connective tissue causing skin hyperextensibility, joint hypermobility,
What are the more common proteoglycans and where are they found?
Perlecan is found in the basement membrane.
Aggrecan and Syndecan are found in cartilage, while Decorin is present in connective tissues
