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
What are elastic fibres made of
microfibrils, elastin and fibrilin
how is stretching reduced
collagen and elastic fibres are interwoven
What are some features of laminins
- multi adhesive proteins
- form a ‘cross like structure’
- can bind to dystroglycan, perlecan and integrins
- has alpha, beta and gamma sub units
- can self associate
- can interact with other matrix components such as type 4 collagen, nidogen and proteogylcans
What problems can laminin defects cause and what are their symptoms (2)
1) muscular dystrophy
symptoms: hypotonia ( decreased muscle tension ), generalised weakness and deformities of the joints
Arises from lack of a2 chain in laminin 2
2) epidermolysis bullosa
What are some features of fibronectins
- multi adhesive proteins
- insoluble extra cellular matrix or soluble plasma protein
- in some cells is continous with the mechanical actin cytoskeleton
- can bind to collagen, heparin and integrins
- can join ligands to cell receptors ( eg collagen can bind to fibronectin which binds to integrins on the cell surface membrane )
- play roles in cell adhesion, migration and formation of blood clots
What are proteoglycans
core proteins attached to 1 or 2 glycosaminoglycan side chains
GAGs are formed of repeating disaccharide units with one of the 2 being an amino sugar
many GAGs are carboxylated or sulfated and so have a high negative charge which attracts Na+ and so water too
Give an example of a basement membrane proteoglycan
perlecan
Give an example of a small leucine rich proteoglycan and the GAG side chain its associated with
Decorin and D ermatan sulfate
Give an example of a cell surface proteoglycan and the GAG associated with it
syndecans 1-4
heparan sulfate
aggregating proteoglycans and the GAG associated with it
aggrecan
hylonuran, keratan sulfate and chondroitin sulfate
What is cartilage
collagen +GAGs trapped in the mesh
What are the 4 types of GAG chains
hyaluronan
chondroitin and dermatan sulfate
heparan sulfate
keratan sulfate
what is the repeating disaccharide unit in hyulauronan
glucuronic acid
N acetyl glucosamine
why can hyulauronan chains have a high volume
high degree of polymerisation - in the range of 10,000 disaccharides
Where can hyulauronan be found
vitreous humour of eyes
synovial fluid of joints
what role does hyulauronan play in the synovial fluid of joints
protects cartilagenous surface from damage
How is hyulauronan spun out
directly from an enzyme embedded in the plasma membrane
What is osteoporosis
with age, aggrecanases and metalloporinases cleave aggrecan, disturbing its cushioning properties
how do fibrotic diseases occur
excessive production of fibrous ECM
Mutations in the protein fibrillin-1 are associated with Marfan’s syndrome which has diverse manifestations. Whare are some potential features of Marfan’s syndrome
Tall and slender build
Spider like fingers
susceptibility to aortic rupture
What properties of the molecule aggrecan means it can resist large compressive forces
highly negative charge due to sulfates (chondroitin and keratan sulfate) and carboyxl group means attracts Na+ which attracts water, acting as a cushion
