L21 – Molecular Composition and Functions of Glomerular barrier Flashcards
(52 cards)
What are basement membranes?
Specialized ECM that underlie all epithelial cell sheets and tubes
What does basement membrane Provide strong connection between?
epithelia and underlying connective tissue
What three core components make up basement membrane?
Type IV collagen
Proteoglycans
Laminin (glycoprotein)
What does BM act as in glomerular?
Filtration barriers between parenchymal cells and connective tissue space
What is the normal GFR range?
90-140mL/min
What is normal Plasma / blood flow rate from renal arteries (Qp) ?
~700 mL/min
What are the 3 Structures that govern transport processes at the glomerular barrier?
Fenetrated glomerular endothelial surface
Glomerular Basement membrane
Podocyte foot processes
What is name of space between podocyte foot processes?
Slit Diaphragm
Fenestrated glomerular endothelial surface (ESL) other name?
Glycocalyx
What is ESL formed by?
Secreted proteoglycans
Secreted glycosaminoglycans
(GAG)
Adsorbed plasma proteins
What is the function of Chondroitin sulfate in ESL?
Negative charge on surface = barrier to prevent passage of charged molecules
What makes up most Proteoglycans found on ESL?
Syndecan core protein + Chondroitin sulfate/ Heparan Sulphate side chains
Glypican core protein + Heparan sulphate side chain + GPI anchor
How can podocytes produce chemicals that affect endothelial glycocalyx?
Podocyte produces :
ang1 >VEGFR1
VEGF > VEGFR2
Chemicals that allow Endothelial glycocalyx to interact with GBM?
a5b1, a5b3
How are collagen molecules arranged?
3 polypeptide chains (α-chains) form triple helix
What is aa sequence of collagen?
repeating triplet sequence “Gly-X-Y” (X, Y = amino acids other than glycine)
Why is glycine in every third position on collagen chain?
small enough to fit into restricted space in center of triple helix, allow tight twisting
What are the 4 steps to intracellular biosynthesis of Type IV collagen?
Pre-procollagen chains are translated
Cleavage of signal peptides to form procollagen α chains
Hydroxylation, Glycosylation
Association of nascent carboxy-terminal propeptide chain (coil around each other)
How is pre-procollagen translated and translocated into ER?
guided by signal peptides to
translocate into ER lumen for intracellular modification
How happens to pre-procollagen to turn into procollagen?
Cleavage of signal peptides (so that they do not go elsewhere after entering lumen of ER) > form procollagen α chains
What intracellular modifications are made before the procollagen form triple helix?
Hydroxylation of certain proline, lysine residues
Glycosylation (add galactose, glucose) of: hydroxylysine, asparagine residues
How is triple helix of collagen stabilized?
Association of nascent carboxy-terminal
propeptide chain (coil around each other)
= stabilize with S-S bond > triple helical procollagen
What supramolecular assembly of Type VI collagen takes place after being exported from cell? (tropocollagen to triple helical domains)
tropocollagens dimerize at Carboxy terminal terminals (NC1) > form tropocollagen dimers
4 tropocollagen dimers aggregate at N-terminal > form type IV collagen tetramer (7S domain)
Lateral association of triple helical domains
What does the structure of collagen do for filtration?
Has big spaces in
between structures for filtration