4.14.2010

1. Mistakes from Last lecturea. Parapoptosis

i. Apaf-1 independent as well as cytochrome cii. Does not activate caspase 9 via apaf-1

iii. It activates an alternative caspase2. ECM

a. Muscleb. Nervousc. Connective

i. types1. Bone

a. Cells secrete ECMb. Osteocytes

i. Mature cells of this cell typeii. Osteoblast – secretes ECM of molecules

2. Cartilagea. Chrondrocytes

i. Mature cells of this cell typeb. Chrondroblasts

i. Secrete ECM of Cartilage3. Loose connective tissue (under epithelium)4. Blood5. Lymphoid tissue

ii. More ECM than cellsd. Epithelial Tissue more ECM than cells

i. Independent of connective tissueii. Made of epithelial cells

1. Attach to basil laminae. Fibroblasts

i. Loose connective tissue3. Skin

a. Epithelial cellsi. Linked by tight junctions to integrins

1. Underneath is loose connective tissue that proveide tensile strength

4. ECM of Loose connective Tissuea. Proteoglycans

i. Made up of a core protein linked to many negatively charged polysaccharides that have a particular structure

1. This structure characterizes them as GAGS – glycosoaminoglycans2. Negative charges attracts water

a. Now the ECM has a fluid-like component to it.b. Presence of proteoglycans will determine how fluid the

ECM is (bones don’t have much)

b. Fibrillari. Types

1. Collagen2. Fibronectin3. Elastin

ii. Provides 1. Strength2. Attachment sites for cell receptors

5. Collagena. Characterized by alpha subunitb. Can combine in different ways to produce the different collagens

6. Synthesis of Collagena. Occurs in the ER lumenb. Contain

i. Prolin1. Heavily hydroxylated – form H bonds as single alpha chains come

to form a triple helix between hydroxylated prolin2. Hydroxylated lysine are also involved3. Scurvy

a. Decrease in hydroxylated proline levelsi. Lack of vitamin c

1. Helps hydroxlate prolinii. Glycine

1. Smallest amino acid2. Every 3rd amino acid in a collagen chain is a glycine

a. Allows close interaction of chains to favor the formation of hydrogen bonds

c. Forms a fibril, about 270, are aligned so they overlap in a region ~ 67nm wided. Once fibrils assemble into a fiber, they are striated in form because of how the

collagen molecule is offset. This allows tensile strength. This is a phenotype of the collagen and why it has a strong tensile strength

7. Type-1 Collagena. Tendonsb. Cornea of eyec. ~95% of collagen in bodyd. Type-1 fiber

i. Interaction between type 1 and type 4 allows a molecule that is rigid and flexible.

e. Mutations in Type-1i. Usually heavily localized in bons

ii. Osteogenesis imperfecta1. Genetic, makes bones brittle.

f. Mutaions in Type-IIi. Chondrodisplasiaa

ii. This collagen is heavily found in cartilageg. Mutations in Type-III Collagen

i. Ehler-Danlos syndrome1. Attachment of blood vessels and joints2. Skin is fragile3. Joints are hypermobile, blistering, skin rupturing.

8. Type-II Fibril Structurea. Tye-II fibril

i. Associates with type-IX with flexible kinksb. As It assembles, primarily in cartilage, n terminus stick out, so the space

generated organizes collagen so it crisscrosses, and inbetween are proteoglycans, creates gel liked structure of cartilage

9. Prolinea.

10. Diseasea. Rheumatoid Arthritis

i. Immune system attacks collagen ii. Normally collagen is not immunogenic

11. Fibronectina. Secreted by fibroblastsb. Important roles out in the connective tissue to help organize connective tissuec. Made of two large polypeptides

i. At COOH terminus, linked by di sulfide bonds to hold the polypeptides together

ii. Binding sites on fibronetiniii. Blood clotting

1. Fibrin binding domaina. Heparin

d. Arginine, glycine, asartate – form RGD sequencei. Used for integrin receptors

e. Collagen Binding Domainf. Heparin and fibring. Integrins nteractct with fibronectin in connective tissue

12. Proteoglycans and Glycosaminoglycansa. Chrondroitin Sulfateb. Keratin Sulfatec. Hyalurnoated. Don’t memorize the combinations of sugars, just know that there are different

combinations of sugars to make different compounds.13. Aggrecan

a. Core protein is heavily concentrated with hyalurnateb. Proteoglycans stick of hyal molecule

i. Hyal organizes the prot glycsc. Found in cartilage

14. Integrinsa. Alpha and beta chain

i. Can vary1. Which can yield a specific function for that integrin

ii. A7b1 – muscular distrophy