extracellular matrix and cell adhesion Hardy Flashcards
5 classes of ECM macromolecules
collagens elastin proteoglycans hyaluronan adhesive glycoproteins
extracellular matrix of connective tissue
fibers (collagen, reticular)
proteoglycans
GAGs
most abundant protein in human body
collagen
which collagen ; 50% of all basal lamina protein
type 4
what other collagen is part of basal lamina
type 7 (VII), 15 (XV), 18(XVIII)
which type of collagen is primary protein of cartilage
type 2
which type of collagen is primary protein of bone?
type 1
which types form long fibrils(tendons, organ capsules, dermis)
1,2,3,5,11
which type associated with fibril ( link collagen fibrils together)
9, 12, 14
this type form anchoring fibrils (bind basal lamina to reticular fibers)
7
this type form networks (basal lamina)
4
collagen into triple helix, repeating amino acid sequence
Glycine - X - Y
X=proline
y=hydroxyproline
most abundant type of connective tissue fibers
collagen fibers
what is absent in scurvy
absence of collagen synthesis
hydroxylases that hydroxylate proline/lysine
mutations that significantly decrease synthesis of pro-collagen chains
Osteogenesis imperfecta type 1
most common cause of OI
Heteroxygous mutations of pro a1 (COL1A1) or pro a2(COL1A2) gene
mutations that result in structural abnormal pro a chains=compromised assembly, abnormal folding
OI type 2-4
this - assembly into procollagen trimers
c-propeptide domain
single base substitution disrupts glycine affects what?
helical domain
bone mineral density decreased - result in fragile/brittle bones
osteopenia
symptoms of OI
osteopenia, bright-blue sclera, grossly discolored,abnormal teeth, hearing loss
mutations in collagen structural genes
Ehlers-Danlos syndrome
what genes are mutated in Ehler-Danols syndrome?
COL1A1, COL1A2, COL5A1, COL5A2
Symptoms of E-D syndrome
joint hypermobility
hyperextensible skin, valvelty in textures, easily scarred
1:5000 live births
extensive network of extremely thin fibers (threadlike)
Reticular fibers
what type of collagen is reticular fiber?
type 3
where those reticular fibers located?
around parenchyma of various organs
abundant in hematopoietic organs( speen,lymph nodes, bone marrow)
what type collagens assemble into sheets?
type 4 and 8
which fiber located in adrenal cortex and lymph node?
Reticular fiber
which fiber is found in mesentery, dermis and artery?
elastic fibers
thinner than collagen fiber; branching pattern.
subject to bending or stretching
elastic fibers
elastic fibers are composed of what?
fibrillin and elastin
how elastic fiber assemble?
fibrillin-1 and fibrilin-2 self assemble after secretion into extracellular space
elastic fiber assembly; lysines condensed into a ring and what covalently cross-links elastins?
desmosine
elastic assembles between what?
microfibers of fibrillin
what gene is (90%) dominantly mutated in marfan syndrome?
fibrillin-1 gene
what is poorly formed in marfan syndrom
elastic fibers
triad of features of marfan syndrome?
skeletal ; long bone
ocular: shifted lens (thickened)
cardiovascular: mitrial valve problem/aortic problem
what is the most dangerous feature of marfan syndrome
weakness of elastic fibers in the aorta
- > enlargement of the vessel (aneurysm)
- ->rupture = fatal consequences
protein + GAG (covalently)
proteoglycans
proteoglycan has more protein or GAG?
GAG
Structural component of ECM
Proteoglycans
what do proteoglycans do?
resiliency to compression
anchor cells to ECM
Bind/sequester some signaling proteins (FGF)
what forms cartilage?
aggrecan aggregates form cartilage
what is GAG?
repeating disaccharide of hexosamine (glucosamine or galactosamine) and uronic acid (glucuronic or iduronic)
GAG forms what?
linear polysaccharides
distinct features of GAG
highly hydrophilic
highly viscous
All gag except hyaluronic acid are?
covalently attached to proteins (proteoglycan)
synthesized in golgi
rich in sulfate
10-40kDa
largest GAG
most ubiquitous GAG
Hyaluronic acid (hyaluronan)
how Hyaluronic acid is synthesized?
it is synthesized into ECM by enzyme(hyaluronate synthase) that is located in plasma membrane
large polypeptide protein in which monosaccharides are covalently attached
glycoprotein (multiadhesive)
glycoprotein contains more protein or GAG?
Protein
features of glycoprotein
specific molecular interaction
simultaneously bind multiple different molecules
‘modules” relaying function or specific binding
what are the glycoprotein, “modules/domains”?
complement-like, cysteine-rich, EF-hand, EGF, fibronctin 1, fibronectin 2, fibronectin 3, fibrinogen, immunoglobulin, lectin
prevalent examples of glycoprotein?
fibronectin, laminin, tenascin
4 primary components of basal lamina?
collagens
laminins
entactin/nidogen
proteoglycans
5 functions of basal lamina
- structural attachment
- compartmentalization
- tissue scaffolding ( regeneration)
- signaling/regulation
- filtration (bidirectional)
glomerular basement ( thick basal lamina) are created by?
capillary endothelial cells podocytes, collagen type 4, proteoglycans glycoproteins
hereditary glomerulonephritis?
alport syndrome
what collagens are affected in alport syndrome?
collagen 4 (alpa 3, 4, 5 genes)
cause/symptoms of alport syndrome
thin and split basement membranes in glomeruli
–> hematuria, proteinuria, progressive kidney failure
anti-glomerular basement membrane disease - autoantibodies “autoimmune disease”
goodpasture’s syndrome
what type of collagens are affected by goodpasture’s syndrome
collagen type 4 (alpha 3)
4 adhesion family
- cadherin family
- immunoglobulin family
- integrin family
- selectin family
