3- ECM 1 Flashcards
(20 cards)
What is the function of the ECM?
Itprovidesphysicalsupport
o Itdeterminesthemechanicalandphysicochemicalpropertiesofthetissue
o It influences the growth, adhesion and differentiation status of the cells and tissues with
which it interacts
o Itisessentialfordevelopment,tissuefunctionandorganogenesis
What is the ECM?
It is a complex network of proteins and carbohydrates filling space between cells
It has both fibrillar and non fibrillar component
What connective tissue makes up the ECM?
Collagens
Types I – III are fibrillar, Type IV is present in the basement membrane (basal lamina)
o Glycoproteins
Fibronectin, fibrinogen, laminins (in the basement membrane)
o Proteoglycans
Aggrecan, Versican, Decorin, Perlecan (basement membrane)
Name gene mutations which effect the matrix proteins
Osteogenesisimperfecta–TypeIcollagen
o Marfan’ssyndrome–FibrillinI
o Alport’ssyndrome–TypeIVcollagen(α5)
o Epidermolysisbullosa–Laminin5(inallthreechains) o Congenitalmusculardystrophy–Laminin2(α2chain)
What gene mutations effect ECM metabolism
Hurler’ssyndrome–L α iduronidase
o Othermucopolysaccharadioses–inabilitytodegradeglycosaminoglycans
What diseases are caused by ECM deposition
Liverfibrosis–cirrhosis
o Kidneyfibrosis–diabeticnephropathy
o Lungfibrosis–silicosis
Give a disorder caused by loss of ECM
Osteoarthritis
Describe collagens
Make up 25% of protein mass, 28 types, coded for by 42 genes, made of 3 chains forming a left handed triple helix
What is collagen 1 made of?
it has two α1 chains and one α2 chain
What is collagen 2 and 3 made from?
Types II and III colagen are homotrimeric, they have the same α chain [α1(II)]3 and [α1(III)]3 respectively
How do collagen fibrils give tensile strength to tissues?
successive layers that are perpendicular to each other
Which amino acids make up collagen?
the chain follows a continuous repetitive pattern of Gly x y, with x often being proline and y is often hydroxyproline Each α chain is around 1000 amino acid residues long in fibrillar collagens
Every third amino acid residue in the α chain is a glycine. It faces the interior of the polypeptide chain because it is hydrophobic and it is the smallest amino acid and thus can fit into the gap
Describe collagen biosynthesis
All newly synthesised collagen chains have non collagenous domains at the N and C terminals. These domains are removed after secretion of the collagen (extracellular) in fibrillation collagens.
The N and C terminals of the procollagen have globular proteins associated with them. A peptidase cleaves them off
Some types of collagen retain these globular ends or part of them
When the collagen fibrils are formed, cross links between the hydroxyl groups of adjacent collagen fibres forming hydrogen bond formation
What do prolyl and lysyl hydroxylases require to work?
Fe2+ and vitamin C
So Vitamin C deficiency (hypovitaminosis C) results in underhydroxylated collagens which means they lack the cross links and aren’t as stable. This means tissues aren’t as stable as they usually would be, causing scurvy
Describe Lysine and proline hydroxylation
The hydroxylation of the lysine and proline amino acids contributes to the hydrogen bond cross link formation between the adjacent collagen molecules
These are done by prolyl and lysyl hydroxylases.
Hydroxylysine and hydroxyproline undergo further modification to form covalent cross links after they are secreted
The type and extent of cross links is tissue specific and changes with age
Describe collagens which do not form fibrils
Types IX and XII collagen associate themselves with fibrillar
Collagens and regulate their organisation.
Type IV collagen is a network forming collagen and is present in all basal laminae, though its molecular constitution varies from tissue to tissue. They assemble into a sheet like network as an essential component of basal laminae
Describe the structure of elastic fibres.
Elastic fibres consist of a core made up of the protein elastin and microfibrils, which are rich in the protein fibrillin.
Elastin contains two types of segments that alternate along the polypeptide chain:
o Hydrophobicregions
o α helicalregionsrichinalanineandlysine(manylysinesidechainsarecross linked)
What is the basement membrane?
flexible, thin mats of extracellular matrix that underlie epithelial sheets and tubes
Where are basement membranes found?
surround muscle, peripheral nerve and fat cells and underlie most epithelia.
They separate the cells from the underlying connective tissue
What is Diabetic nephropathy?
accumulation of extracellular matrix that causes a thickened kidney
glomerulus. The basement membrane is thickened, restricting renal filtration by impinging
capillaries
