Pintar - ECM

Question 1

Stroma

Answer 1

Group of strands that make up the ECM

Question 2

3 regions of the basement membrane

Answer 2

• lamina rara, lucida, or interna - top layer made up of laminin 5 and type XVII collagen - made by epithelium
• lamina densa - more dense middle layer made up of laminin 1 and type IV collagen - made by epithelium
• lamina reticularis - bottom layer made up of fibroblasts and type III collagen - made by underlying connective tissue cells such as fibroblasts

Question 3

Collagen

Answer 3

Very abundant protein in the body. Often three helixes are wrapped around each other to make a triple helix rope. The structure of each helix is generally Gly-X-Y. This is good because Gly just has a H atom as it’s R group so it can be shoved between the two other groups. Often the X and Y are proline and lysine, which can be hydroxylated - help for H bond formation (strong structure but very sensitive to mutations).

Question 4

types of 1)fibril forming

Answer 4

I-bones, skin, tendons, ligaments
II-cartlidge, invertebral disc
III-skin, blood vessels, internal organs, can bind silver only due to increased carbohydrate
V

Question 5

Biosynthesis of fibril forming collagens

Answer 5

Collagen ends up outside the cell. Therefore they will begin their synthesis in the cytoplasm. N-terminus will bind SRP. It will be delivered to the ER and be delivered to the cell. 1) There are extension peptides that are part of the primary structure of collagen. They don’t allow for self-assembly into a higher order structure within the ER and golgi. 2) The actual parts of the chains (non-extension part) then get hydroxylated using Vitamin C as a cofactor (that is why sailors got scurvy). Deficiencies of Vitamin C does not allow for collagen to be turned over so you lack strong collagen and teeth fall out. 3) Then the hydroxyl groups are glycosylated. 4) Then the triple helix forms still with the extension peptides and it is excreted from the cell as “procollagen.” 5) The extension peptides will then be cleaved and our new molecule is “tropocollagen” which is a fibril.

Question 6

2) fibril associated

Answer 6

these collagens decorate the outside of fibril fibers. An example is Type IX collagen which decorates the outside of Type II collagen. In type II collagen, the extension peptides are usually retained and the helix is a little less rigid. If mutated can lead to epiphyseal dysplasia, which leads to arthritis.

Question 7

3) Network forming collagen

Answer 7

Major collagen of the basal lamina. Extension peptides are not cleaved. Because the N termini will go above and below the plane, it will create some sort of meshwork that looks like a “chicken-wire” array.

Question 8

Type VII and Type XVII

Answer 8

• Type VII is another network forming collagen. They are made up of monomers. The monomers from the Type VII collagen interact to make a dimer. The dimers interact between the stroma and the lamina densa and they basically keep the stroma stuck to the lamina densa. If a mutation in this, both the lamina densa and the epithelial cells will be pealed away.
• Type XVII helps bind the lamina densa to the epithelial cells. Mutation in this will cause a blistering disease where the epithelium will peel away but the basement membrane will stay intact.

Question 9

elastin

Answer 9

cross-links with each other. Assembles extra-cellularly. Stretches much like a rubber band. Tissues that require a lot of elasticity are generally high in elastin fiber content. Can be interspersed with collagen fibers.

Question 10

Marfan Syndrome

Answer 10

Mutation in the fibrillin gene. Causes an overgrowth and lengthening in the limbs. Often have long appendages. Aorta tends to be distended and has a possibility of rupturing. Abe Lincoln was though to have this.

Question 11

Glycosaminoglycans

- 3 types

Answer 11

Made up of sugar molecules. Repeating dissacharrides of uronic acid and an amino sugar. At physiological pH the carboxyl group is negatively charged. Because of this the sugar molecules spread out as far as they can so they are generally long fibers. They attract water. A major component of synovial fluid and vitreous humor in the eye.

• Hyaluronic acid - not sulfated, not attached to protein
• Chondroitin sulfate and Heparan sulfate - both sulfated and attached to proteins

Question 12

Aggrecan

Answer 12

A complex proteoglycan made up of Type II and Type IX collagen. It is an example of a sulfated glycosaminoglycan that is attached to protein. It is found in the cartilage. It is attached, non-covalently to a molecule of hyalouronic acid. Provides mechanical support.

Question 13

Syndecans

Answer 13

Has transmembrane domain. Has heparan sulfate (glycosaminosulfate) attached to the core protein. A mechanism in which the outside of the cell can communicate with the inside of the cell using the sugar chains. Can also bind growth factors and present to receptor.

Question 14

Adhesive glycoproteins

Answer 14

Laminin and Fibronectin
Basically have modular binding domains on their chains so that parts of the ECM can bind.
Mediate attachment between cells to their outside environment

Question 15

perlecan

Answer 15

proteoglycan found with type IV collagen and laminin in the basementt membrane.

Question 16

Integrins

Answer 16

Are dimers with an alpha and beta chain. They are transmembrane proteins so they can interact with things on the outside and inside of cells. Has an RGD sequence that promotes the adhesion to laminin and fibronectin. INTEGRINS ARE NOT ALWAYS IN AN ACTIVE CONFORMATION. Once the substrate is bound, integrins cluster. They bind the cytoskeleton indirectly through a network of proteins. Focal adhesion forms at site of bound integrin via Rho GTPase. This recruits a whole bunch of signaling molecules such as FAK and autophosphorylation of tyrosine molecules.

Question 17

Major classes of integrins

Answer 17

There are 9 types of beta and 14 types of alpha. 24 dimer classes found. However, they are generally classified by the beta chains.

• B1 = bind to ECM molecules
• B2 = bind to molecules on the endothelial surface (WBC) - Disease in B2 cause “leukocyte adhesion deficiency”.
• B3 = bind platelets, fibrinogen, help initiate clots - mutation leads to Glanzmann’s disease in which fibrinogen can’t be bound and we don’t clot properly
• B4 = found in hemidesmosomes and bind specific laminins. Binds Laminin 5. Mutations in Laminin 5 will cause peeling away of the basement membrane and blistering.

Question 18

How does integrin become active/inactive

Answer 18

Usually there is an independent signaling mechanism in a different receptor. Once this other receptor has the proper lligans bound, an intracellular signaling cascade is initiated. This interacts with the internal parts of the integrin molecules, which causes a conformational change and activates the integrin molecules.

Question 19

ground substance

Answer 19

macromolecular components. Ground substance + cells = connective tissue