2.7 Extra cellular matrix Flashcards
What is an extra cellular matrix
complex network of proteins and carbohydrates filling spaces between cells
composed of fibrilar and non fibrilar parts
What are the key functions of the ECM (4)
- provides physical support
- determines mechanical and physiochemical properties of the tissue
- influences the growth, adhesion and differentiation of the cells and tissues with which it interacts
- essential for tissue function, organogenesis and development
Which collagens are fibrilar
1-3
Which collagen is used in the basement membrane
collagen 4
What are the 3 multi adhesive proteins
Laminins, fibrinogen and fibronectin
What are 4 proteoglycans
aggrecan
decorin
versican
perlecan
What is the ECM part that is disturbed in 1)osteogenesis imperfecta
2) Marfans syndrome
3) Alports syndrome
4) epidermolysis bullosa
5) congenital muscular dystrophy
1) Collagen 1 where cysteine is coded for
2) Fibrilin 1
3) Type 4 collagen
4) Laminin 5
5) Laminin 2
What are the symptoms of Alports syndrome
progressive loss of kidney function
hearing loss
What are the causes and symptoms of Marfans syndrome
problems in gene coding for fibrilin
spider like fingers
susceptible to aortic rupture
What is the arrangements of collagen fibrils in the skin, mature bone and cornea
Successive layers are at right angles to each other to resist tensile force
What type of collagen is a heterotrimer
collagen 1
What is the i) characteristic repeat in collagen and 2) what secondary structure does this lead to
i) gly -x - y with x and y often being proline and hydroxyproline
ii) glycine is small enough to occupy the interior space and so forms a left handed helix
What are non collegenous domains and in which cases are they removed
All newly synthesized collagen chains have non collengenous domains at the N and C terminals
In fibrilar collagen, they are removed after secretion but not so in non fibrilar collagen
What are the 9 stages of collagen assembly (and where do they happen )
1) formation of pro alpha chain ( in ER/ golgi)
2) hydroxylation of proline/lysine ( in ER/ golgi)
3) Glycosylation (of hydroxlysine in ER/ golgi)
4) self assembly of pro alpha chains ( in ER/ golgi)
5) procollagen triple helix formation ( in ER/ golgi)
6) secretion (in secretory vesicle)
7) Cleavage of propeptides (forming a collagen molecule )
8) self assembly into fibrils (10- 300nm long )
9) self aggregation into fibres (0.5 to 3 micrometers long)
What are the 2 types of cross linking formed
1) intermolecular - between hydroxyl and carboxyl group
2) intramolecular - between collagen molecules
How does hydroxylation happen
lysine and proline can by hydroxylated by lysyl and prolyl hydroxylases which require vitamin C and Fe2+ as co factors
which contributes to interchain hydrogen bond formation
What is scurvy
reduced vitamin c intake
reduced hydroxylation of proline and lysine ( as vitamin C is a co factor )
reduced tissue stability
What is Ehlers Dahl syndrome
group of inherited connective tissue disorders
symptoms are stretchy skin and loose joints
due to disorders that negatively effect:
collagen production
collagen structure
collagen processing
What do collagens 9 and 12 do
regulate the organisation of collagen fibrils
how do collagen 4 organise
sheets that form network that is called a basement membrane
What are the 4 stages of collagen molecule assembly
1) have a monomer with a collagenous and non collagenous end
2) non collogenous ends attach to form a dimer
3) a tetramer is former
4) a supramolecular aggregate is formed
What is diabetic nephropathy
Accumulation of ECM leading to a highly thickened basement membrane
restricts renal filtration and can cause renal failure
What disorder can arise from fibrilin
Disorders of fibrilin 1 lead to marfans leading to :
1) increased susceptibility to aortic rupture
2) spider like fingers
what is collagen important for
high tensile strength
