Animal ECM Flashcards
(29 cards)
What are the three main functions of the ECM?
An inert framework/scaffold
Functions in signalling
- Perception
- Transmission
Functions as a co-ordinator of cellular activities
- Growth and motility
- Morphogenesis
What are the components of the animal ECM?
Draw it out!
Epithelial cell sheet
Basal lamina
macrophages
fibroblast
collagen fiber
capillary
elastic fiber
mast cell
glycosaminoglycans
proteoglycans
glycoproteins
What are the three components of the animal ECM?
Basal lamina
- Platform for epithelia and other groups of organised cells to rest upon (e..g muscle)
- Tightly bound to cells by proteins in the plasma membrane
Loose connective tissue
- Highly elastic connective tissue
- bedding on which small glands and epithelia connects to basal lamina around cells
Dense connective tissue
- Bone, cartilage, tendons.- components of skeletal system
- contains few cells, comprised almost entirely of inflexible ECM
What are the 5 building blocks?
Collagen : protein, long fibres/porous sheets
Glycosaminoglycans
Hyaluronan
Proteoglycans - core of protein with attached glycosaminoglycans
Elastin - an elastic protein
What are the structural tensile fibres in the meshwork made of?
Collagen…
Talk about collagen
Key words
Fibrous
Glycine
Rich in two things that lends stability to the helix
Long - how long
Thin - how thin?
A …. helix?
Each chain how many amino acids?
It is an insoluble, fibrous protein
It has glycine at every three amino acids
Rich proline and hydroxyproline
300nm long
1.5nm - really thin!
A triple right hand helix
1050 amino acids in each chain
Describe collagen gene structure
The gene encodes protocollagen
The Glycine-aa-aa (GXY) primary amino acid sequence repeats are encoded in many small exons
Each exon is based on a so-called primordial unit comprised of 54 nucleotides encoding 6 GXY repeats
Evolutionary implications - ancestral collagen contained 6 repeats
Omg, how does collagen biosynthesis work?
ER (1-4)
1: synthesis and translocation of pro alpha chain
2: proline and lysine hydroxylation - vitamin C
3: Glycosylation of hydroxylysines
4: Self-assembly of procollagen triple helix
5: Golgi: N-linked glycol modifications
6: Secretory vesicles: transfer to PM
7: ECM: cleavage of pro peptides by extracellular proteases
8: ECM: self-assembly to collagen fibril
9: ECM: aggregation of fibrils into fibre
What’s so important about ascorbate?
Ascorbate - ascorbic acid allows hydroproxylation of collagen which is important in structural integrity .
Ascorbate deficiency leads to a weakening of collagen and therefore the ECM and therefore connective tissues
What are the three functional families of collagen?
Fibril forming - bone, skin tendon, ligaments, cornea, internal organs, skin, blood vessels
Fibril associated - cartilage, tendon, ligaments, other tissues
Network forming - basal laminae,
What mutations that cause disease show the importance of fibril forming collagen ?
There are three diseases
Osteogenesis imperfecta
Chondrodysplasia
Ehlers-Danlos syndrome
Osteogenesis imperfecta - affects type I collagen, brittle bone disease, autosomal dominant, lethal in severe cases. definitely crippling, mutations changing Gly residues in the C-terminus indicate their importance
mutations in the alpha 2 chain are much less “damaging”
Chrondrodysplasia
affects type II collagen
bone and joint deformities
Ehlers-Danlos syndrome
Affects type III collagen,, fragile skin and blood vessels and hypermobile joints
What is fibril associated collagen?
What is it important for?
Important for interaction with other molecules in the ECM - determinants of the ECM structure
Especially important in cartilage, ligaments, and tendon
Structure interrupted by one or two non-helical domains
Differential tissue distribution and collagen-collagen interactions
i.e. type IX with type II in cartilage, cornea, whereas type XII with type I in tendons and other tissues
What are the principal ingredients of gelatin
Fibril-forming and fibril-associated collagen
Describe the structure of network forming collagen
Draw a diagram!
Three Type IV network forming collagen chains form a 400nm triple helix with a large globular C-terminus
GXY sequences interrupted with non-helix formers - introduces flexibility into the molecule
How does type IV collagen molecules assemble to form basal laminae?
Clue: sheetlike meshwork, rather than rods
They assemble into a sheetlike meshwork, rather than rods to help form basal laminae
Monomers, rapid head to head associations via c terminal globular domains
lateral associations via triple helical domains to form a sheetlike meshwork
N-terminal tails projecting above and below plane of meshwork
sheetlike polygonal meshwork - slow covalent associations via N-terminal tails to form a stacked network of sheets
Multilayered network
What are the interactions between the major components of the basal laminae?
Draw the schematic that shows interactions between the four
There are 4 major components
type IV collagen
Perlecan
Entactin
Laminin
What does the basal laminae do?
Flexible and thin mats of specialised ECM that underlie all epithelial cell sheets and tubes
Surround individual muscle, fat, and Schwann cells
Structural and filtering roles
and determine cell polarity
Influence: cell metabolism organise proteins in adjacent PM induce cell differentiation serve as "highways" for cell migration
How is the ECM really essential for cell migration and “retaining” cells?
How does a tumour demonstrate this?
Tumour starts as a single spontaneously modified cell
Mass of tumour cells,
tumour contained within tissue by ECM - relatively benign tumour
Invasive cells breach basal laminae of tissue and the blood vessels, highly invasive metastatic tumour …..
How does ECM allow for stretching?
Elastic fibres
Some elasticity has to be built in the system e.g. skin, lungs, blood vessels
Elastin is a highly HYDROPHOBIC protein (750 aa long)
Proline and glycine rich (like collagen), BUT NOT glycosylated and contains little hydroxyproline and no hydroxylysine (unlike collagen)
Forms cross linked fibres
What are the two complex polysaccharides and what do they do?
Glycosaminoglycans (GAGs)
Proteoglycans
Disordered voluminous compression-resistant components
- Fluid mucous secretions
Provides a highly flexible, hydrated, extracellular coating
- compression resistant
- protease resistant
Original eukaryote may have surrendered a rigid cell wall in favour of a snotty, glycosylated exterior coating
- resistant to invasion and proteolytic attacl
- suitable for ensnaring and engulfing cellular prey
Glycosaminoglycans
A = a Uronic acid
glucuronic acid
galacturonic acid
B = amino sugar
N-acetylglucosamine
N-acetylgalactosamine
Hyaluronan - the simplest and most abundant GAG
regular repeats of 25,000 glucuronic acid and N-acetylglucosamine disaccharides
What are the properties of GAGs?
Polysaccharide chains are too inflexible to fold tightly
strongly hydrophilic
adopt extended conformations and occupy a huge volume relative to their mass
form gels at even low concentrations
High density of negative charges attracts sodium - osmotic effect increases swelling / turgor pressure enabling it to withstand large compressive forces
What about the proteoglycan component?
Extra info:
Glycan linker and GAG are added in Golgi apparatus
Most GAGs are attached to proteins via serine or threonine
O-linked glycosylation with Glycosaminoglycan (GAG)
Unlike glycoproteins (which are typically 1-40% carb by weight), the proteoglycans contains WAY more carbs by weight (up to 95% carbohydrate)
GAGs are usually heavily sulphated
What is a GAG sandwich?
Proteoglycans can associate with other glycosaminoglycans
There is a GAG core
then a proteoglycan core (green branches), then GAG branches
