ECM Structure & Function

Question 1

Type I Collagen

Answer 1

Most ABUNDANT; found in bone, tendon and skin
(Defect: Osteogenesis imperfecta);
LARGE diameter

Question 2

Type II Collagen

Answer 2

Found in dry weight cartilage;

Mutation: Chondrodysplasia

Question 3

Type III Collagen

Answer 3

Widely DISTRIBUTED IN BODY; found in skin and aorta
A.k.a “reticular fibers”
(Defect: Elastoderma or Ehler’s Danlos-Type 3)

Question 4

Type IV Collagen

Answer 4

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

Question 5

Type VII Collagen

Answer 5

Network-forming, non-fibrillar
Found in anchoring fibrils
Below stratified squamous epithelia
(Defect: Epidernolysis Bullousa - whole epithelial layer and lamina densa peel off)

Question 6

Type IX Collagen

Answer 6

Decorates the cartilage, outside of Type 2 collagen

Defect: Epiphyseal dysplasia

Question 7

Type XVII Collagen

Answer 7

Transmembrane Type
Connect basement membrane with epithelium
Near Anchoring filaments in lamina lucida (top)
(Defect: Bullous Pemphigoid)

Question 8

Hyaluronic Acid

Answer 8

This Glycosaminoglycan (GAG) has a NEGATIVE charge at body pH, is not sulfated, and is found as a free fluid.

Question 9

Glycosaminosglycans, GAG

Answer 9

Complex sugars that bind to water,
Long and unbranched, alternating chains of NacGal and NacGlu
Ex: Chondroitin Sulfate, Heparan Sulfate, Hyaluronic Acid

Question 10

Proteoglycans

Answer 10

A bunch of GAGs attached to a core protein on cell surfaces

Ex: aggrecan, perlecan, syndecan-1

Question 11

Perlecan

Answer 11

A proteoglycan found in the basal lamina,
Fewer GAG side branches of heparan sulfate attached
Functions for structure and filtration in ECM

Question 12

Syndecan-1

Answer 12

Found in fibroblast and epithelial cells
Involves few GAG chains of chondroitin and heparan sulfate
Function in growth factor binding and signaling pathways

Question 13

Aggrecan

Answer 13

HUGE prototype proteoglycan found in cartilage
Function for mechanical support like a cushion for bones
Backbone = hyaluronan,
branches = chondroitin sulfate,
sub-branches = keratin sulfate

Question 14

Integrins

Answer 14

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!

Question 15

Beta 1 Integrins

Answer 15

UBIQUITOUS, link fibronectin to actin
Leukocyte-integrin Activation
Involved in regulation of FAK (intracellular pathways)
Acts as a receptor for laminin

Question 16

Beta 2 Integrins

Answer 16

Bind superfamily counter-receptors on WBCs
Leukocyte-integrin activation
(Defect: Leukocyte adhesion deficiency - slippery WBC’s, no binding to endothelium in blood vessels)

Question 17

Beta 3 Integrins

Answer 17

Bind fibrinogen in clotting process, expressed on platelets

Defect: Glanzmann’s Disease - platelets don’t bind fibrinogen, therefore no clotting

Question 18

Alpha-6-Beta-4 Integrins

Answer 18

Expressed on hemidesmisomes of epithelium
Anchors intermediate filaments like keratin on epithelium too
Can also bind fibrinogen

Question 19

Basement Membrane

Answer 19

A.k.a. “Parenchyma” if epithelium attached is specialized
Sharp 3-layered membrane between epithelium and CT
Layers: lamina lucida, lamina densa, lamina reticularis

Question 20

Lamina Lucida

Answer 20

“Glue to the epithelium” - anchors epithelium
Few fibronectin and Type 5 laminin
Involves Type 17 Collagen

Question 21

Lamina Densa

Answer 21

“Dense, Complex Network”

Type 4 Collagen in lamina densa + laminin 1 + perlecan + nidogen

Question 22

Lamina Reticularis

Answer 22

“Anchor to the Stroma” - binds basement to CT
Type 3 Collagen (reticular fibers), also involves Types 1 and 7
Includes proteoglycans and fibronectin

Question 23

Collagen Features

Answer 23

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

Question 24

What co-factor is needed for stability of collagen alpha chains? What disease results from it’s deficiency?

Answer 24

Vitamin C,

Scurvy - lack of hydroxylation on proline and lysine causes breakdown of pro-collagen fibril