ECM Structure & Function Flashcards
Type I Collagen
Most ABUNDANT; found in bone, tendon and skin
(Defect: Osteogenesis imperfecta);
LARGE diameter
Type II Collagen
Found in dry weight cartilage;
Mutation: Chondrodysplasia
Type III Collagen
Widely DISTRIBUTED IN BODY; found in skin and aorta
A.k.a “reticular fibers”
(Defect: Elastoderma or Ehler’s Danlos-Type 3)
Type IV Collagen
Network-forming collagen, non-fibrillar, sheetlike
Found in lamina densa of basement membrane (middle), Near anchoring fibrils attributes to mesh work
Retain C- and N-terminal extensions; allows binding
Type VII Collagen
Network-forming, non-fibrillar
Found in anchoring fibrils
Below stratified squamous epithelia
(Defect: Epidernolysis Bullousa - whole epithelial layer and lamina densa peel off)
Type IX Collagen
Decorates the cartilage, outside of Type 2 collagen
Defect: Epiphyseal dysplasia
Type XVII Collagen
Transmembrane Type
Connect basement membrane with epithelium
Near Anchoring filaments in lamina lucida (top)
(Defect: Bullous Pemphigoid)
Hyaluronic Acid
This Glycosaminoglycan (GAG) has a NEGATIVE charge at body pH, is not sulfated, and is found as a free fluid.
Glycosaminosglycans, GAG
Complex sugars that bind to water,
Long and unbranched, alternating chains of NacGal and NacGlu
Ex: Chondroitin Sulfate, Heparan Sulfate, Hyaluronic Acid
Proteoglycans
A bunch of GAGs attached to a core protein on cell surfaces
Ex: aggrecan, perlecan, syndecan-1
Perlecan
A proteoglycan found in the basal lamina,
Fewer GAG side branches of heparan sulfate attached
Functions for structure and filtration in ECM
Syndecan-1
Found in fibroblast and epithelial cells
Involves few GAG chains of chondroitin and heparan sulfate
Function in growth factor binding and signaling pathways
Aggrecan
HUGE prototype proteoglycan found in cartilage
Function for mechanical support like a cushion for bones
Backbone = hyaluronan,
branches = chondroitin sulfate,
sub-branches = keratin sulfate
Integrins
Regulate FAK (focal adhesion kinase) to enable intracellular pathways (such as in leukocyte extravasation)
Affinity is important for CLOTTING and LEUKOCYTE MIGRATION
Composed of dimers with an RGD sequence that bind together
How to activate: Separate cytoskeletal tails; FLEX THEM OUT!
Beta 1 Integrins
UBIQUITOUS, link fibronectin to actin
Leukocyte-integrin Activation
Involved in regulation of FAK (intracellular pathways)
Acts as a receptor for laminin
Beta 2 Integrins
Bind superfamily counter-receptors on WBCs
Leukocyte-integrin activation
(Defect: Leukocyte adhesion deficiency - slippery WBC’s, no binding to endothelium in blood vessels)
Beta 3 Integrins
Bind fibrinogen in clotting process, expressed on platelets
Defect: Glanzmann’s Disease - platelets don’t bind fibrinogen, therefore no clotting
Alpha-6-Beta-4 Integrins
Expressed on hemidesmisomes of epithelium
Anchors intermediate filaments like keratin on epithelium too
Can also bind fibrinogen
Basement Membrane
A.k.a. “Parenchyma” if epithelium attached is specialized
Sharp 3-layered membrane between epithelium and CT
Layers: lamina lucida, lamina densa, lamina reticularis
Lamina Lucida
“Glue to the epithelium” - anchors epithelium
Few fibronectin and Type 5 laminin
Involves Type 17 Collagen
Lamina Densa
“Dense, Complex Network”
Type 4 Collagen in lamina densa + laminin 1 + perlecan + nidogen
Lamina Reticularis
“Anchor to the Stroma” - binds basement to CT
Type 3 Collagen (reticular fibers), also involves Types 1 and 7
Includes proteoglycans and fibronectin
Collagen Features
A. Triple-stranded helix
B. Gly-X-Y repeat
*X/Y = proline, lysine (which can be hydroxylated)
C. Extent of Post-translational modification (leads to variety in function)
*Ex: N/C-termini retained in Type 4, 9 Collagen to allow complex binding in Lamina densa
What co-factor is needed for stability of collagen alpha chains? What disease results from it’s deficiency?
Vitamin C,
Scurvy - lack of hydroxylation on proline and lysine causes breakdown of pro-collagen fibril
