ECM Flashcards
two regions of ECM accumulation:
basal lamina (basement membrane) - subdomains of lamina interna/rara/lucida and lamina densa
stroma (deepest part of basement membrane - lamina reticularis) and connective tissue
three distinct regions of basement membrane from superficial to deep
lamina lucida/rara/interna
lamina densa
lamina reticularis (sublamina densa)/ stroma
name 4 major macro molecular components of ECM
- structural components: collagen (strength) and elastin (resilience)
- glycosaminoglycans (GAGs): complex sugars, bind water to resist compression
- proteoglycans: GAG + protein (covalent bond)
- adhesive glycoproteins: fibronectin and laminin
what are the two major adhesive glycoproteins of ECM
fibronectin and laminin
most abundant protein in body is? what is its structure?
collagen
monomer of single helix, procollagen of triple-helix, procollagen assembles into fibrils
repeating sequence of every third glycine, which fits inside helix and bond with H
many proline and lysine that can be hydroxylated to contribute to H bonding
4 major collagen classes
- fibril-forming: most abundant, found everywhere
- fibril-associated: found in cartilage
- network-forming: found in basal lamina
- transmembrane: found in hemidesmosomes
major types of fibril-forming collagen? (3)
type I: most common, found ubiquitously
type II: cartilage, invertebral disc, vitreous humor (eye)
type III: skin, blood vessels, internal organs, aorta
what do osteogenesis imperfecta, chondrodysplasia, and Ehler-Danlos syndrome have in common>
tissue-specific diseases associated with mutations in fibril-forming collagens
osteogenesis imperfecta (brittle bone) - Type I (everywhere)
chondrodysplasia - Type II (cartilage)
Ehler-Danlos syndrome (aneurism) - Type III (aorta, blood vessels)
describe basic biosynthesis of fibril-forming collagens
- alpha chain enters secretory pathway, becomes hydroxylated (Vitamin C dependent process)
- glycosylation
- self-assembly of 3 pro-alpha chains
- procollagen triple helix formation
- secretion as pro-peptide
- cleave of propeptides into tropocollagen
- self assembly into fibril
what would happen to a a patient’s ability to synthesize collagen if they have scurvy?
scurvy due to vitamin C deficiency
vitamin C required for hydroxylation of alpha chain
reduced collagen formation
[single glycine mutation in primary structure can also alter collagen helix and reduce collagen synthesis]
what type of collagen is reticular
Type III (aorta, skin, blood vessels, internal organs) (fibril forming)
more carbohydrates, thinner fibrils, more branched, fewer bundles
what two classes of collagen associate to form cartilage (bonus if you can add collagen type)
Fibril forming collagen (Type II)
and
Fibril-associated collagen (Type IX)
Fibril-associated collagen decorates outside of Type II (fibril forming) collagen fibrils in cartilage - interrupts triple helix to form a hinge important for joint integrity
epiphyseal dysplasia is due to a mutation in what kind of collagen?
fibril-associated collagen (Type IX) - decorates Type II (fibril forming) collagen in cartilage, important for joints
mutation leads to arthritis
what is the major collagen of the basal lamina
Network-forming collagen (Type IV collagen)
multilayered chicken-wire array
C and N termini intact (not cleaved)
collagen mutations are also implicated in blistering diseases (like cell junctions). Contrast the effect of Type XVII (17) collagen and Type VII (7) mutations
Type XVII (17) collagen is transmembrane protein —> mutation causes blistering between epithelium and basement membrane
Type VII (7) collagen is network collagen forming anchoring fibrils connecting lamina densa with connective tissue —> mutation causes blistering below basement membrane
which of these are TRUE?
a. type III collagen has specific staining properties from increased CHO bonding
b. networking forming collagen retain extension peptides during assembly
c. post-translational processing of collagen occurs intracellularly
d. Type I, II, III collagens can all form fibrils
TRUE:
a. type III collagen has specific staining properties from increased CHO bonding (*reticular)
b. networking forming collagen retain extension peptides during assembly
d. Type I, II, III collagens can all form fibrils
c. post-translational processing of collagen occurs EXTRACELLULARLY
most assembly of elastic fibers is [intra/extra]cellulary?
extracellularly
elastin monomers are cross-linked to provide resilience
what stain can be used to reveal elastin fibers
ocrein stain
what is the presentation and cause of Marfan syndrome
Fibrillin 1 mutation
increased length of appendages, chest deformity, aorta prone to rupture (AD inheritance)
lack of recoil during development because of defect in elastin (Fibrillin is glycoprotein essential for elastin formation)
what disorder does a mutation in Fibrillin 1 cause
Marfan syndrome: long appendages/limbs, aorta prone to rupture, due to lack of recoil during development
(defect in elastin)
cause and presentation of Epidermolysis bulbosa
Type VII collagen anchoring fibrils disrupted
epithelium and basement membrane peeled away
structure of glycosaminoglycans (GAGs)
repeating disaccharides (amino sugar and uronic acid)
negative charge (COOH and SO4/sulfate group)
binds water (osmotically active)
resist compression - found in joints, vitreous humor (places where there is a lot of water)
3 major classes of GAGs (glycosaminoglycans)
- hyaluronic acid: non-sulfated, NOT covalently attached to protein
- chondroitin sulfate: sulfated (duh), covalently attached to protein
- heparan sulfate: sulfated (duh), covalently attached to protein
what is the major proteoglycan found in cartilage and what is its structure?
aggrecan: protein + chondroitin sulfate (covalent link)
also has hyaluronic acid present (with non-covalently bonded protein)
aggrecanopathies —> skeletal disease
*proteoglycan = GAG + protein
