Extracellular matrix Flashcards
Semester 1 year 1
What is the extracellular matrix and what does it regulate?
-extracellular meshwork of proteins + hydrated macromolecules
-regulates: migration, tissue integrity + cell shape, proliferation, differentiation
Describe the appearance of the extracellular matrix
-collagen + elastic fibres to make skin robust
-sugar chains to hold water
-basal lamina
What are the different types of extracellular matrix?
-fibrous proteins - structural proteins (collagens + elastin)
-adhesion proteins (fibronectin + laminin)
-hydrated macromolecules
Describe the structure of collagens
-repetitive structure - have glycine-proline-hydroxyproline triplet repeats
-triple helix - 3 different alpha peptide chains align
What produces collagens?
Fibroblasts + epithelial cells
What is an example of a disease caused by a collagen defect?
Ehlers-Danlos syndrome - leads to degradation of skin integrity
Describe how a collagen fibre is made
-pro-𝛼 chain is synthesised
-proline + lysine residues in the chain are hydroxylated
-hydroxylysines in the chain undergo glycosylation
-self assembly of 3 pro-𝛼 chains
-a procollagen triple helix is formed + secreted out of the cell
-propeptides are leaved
-self assembly to form fibrils
-aggregation of collagen fibrils to form a collagen fibre
What is elastin made up of?
-subunits of tropoelastin
-held together by cross-links - ensures maximum stretch
What allows the formation of cross links in elastin?
Lysyl oxidase
Why is elastin fragile?
-as it stretches, it deforms
-makes it susceptible to rupture
Describe the appearance of elastin when stretched and relaxed
-relaxed = molecules are coiled + close
-stretched = molecules are straighter
Does elastin gain or lose structure when stretched?
-gain
-has more uniform elasticity across its extension length
What is fibrillin?
The scaffold over which elastin will be laid down
What is an example of a disease caused by a fibrillin defect?
Marfan syndrome - fibrillin deformation means tension not applied to bones, resulting in longer limb length
What are GAG’s Glycosaminoglycans?
-disaccharide chains typically 70-200 units long
-highly charged so hold water effectively
-serine is substituted for a hydroxyl group
Describe the structure of hyaluronan complexes
-hyaluronan = large sugar that runs through main core off which aggrecans branch off
-aggrecan = sugar chain with protein core
What are the different adhesion glycoproteins?
-laminin
-fibronectin
-integrins
What is laminin?
-makes up the basal lamina
-epithelial cells sit on basal lamina + form epithelium
-has many functional domains as it needs to interact more with other molecules
What is the structure of fibronectin?
-has many domains
-forms disulfide bonds to link to itself
-has self-association motifs
-has collagen binding domains
-has cell binding domains, so will interact with integrins on the surface of cells
What are integrins, what is their structure and how do they work?
-transmembrane receptors that allow cells to stick to another molecule
-made up of an alpha + beta subunit
-bind matrix through divalent cations
-removal of cations cause cells to detach
What do focal adhesions do?
Link the cytoskeleton (actin + myosin) to the extracellular matrix
Describe the components of a focal adhesion
-integrin binds to extracellular matrix + acts as transmembrane receptor
talin protein binds to cytoplasmic domain of integrin to begin link to cytoskeleton
-talin binds to vinculin which binds to actin
-talin also binds to focal adhesion kinase (FAK) - adhesion to matrix activated kinase to get a signalling response
What is the major 𝛽 subunit of actin, what does it pair with and what does its knockout result in?
-𝛽1 integrin is major 𝛽 subunit
-pairs with lots of different 𝛼 integrins
-knockout = embryonic lethal
What do 𝛼5 and 𝛽1 integrin make and what does a knockout result in?
-makes a fibronectin receptor
-knockout = embryonic lethal
