4.16.2010

1. Recap from last lecturea. Proteoglycan structure in cartilage

i. Aggrecan1. Hyaluronate core with proteoglycans linked to it.2. Made of hyaluronate, a GAG, linked to proteoglycans3. Made of hyaluranate, a GAG, linked to lots of proteoglycans

ii. GAGs form proteoglycans1. Chrondroitin Sulfate

a. One choice is N acetyl galactosamine is the amino sugari. Can be used to make GAGs

2. Keratan a. Another choice in the keratin sulfate is N acetyl gluconate

(N acetyl glycosamine)i. Can be used to make GAGs

iii. Link with sugar acids that help form GAGs1. Galactose2. Glucyronate

b. Hyaluronate is a galactosamine itself in repeating unitsi. Linked up with proteoglycans

2. Integrinsa. Made of two subunits

i. Alpha 1. 9 different alpha subunits identified

ii. Beta1. 24 different ones

iii. can also have many formsb. The EXC receptor

i. Extracaellular1. Globular region for RGD sequence or binding sites on laminin

c. Alpha Helixi. Transmembrane region

d. Binding site for taline. A5B1 ubiquitousf. Fibronection component of matrix below laminag. LFA-1h. Leukocyte Adhesion Deficiency

i. WBC can’t migrate to tissue to deal with infectionii. Neutrophiles move to the site first

1. If they can’t migrate, then the bacteria, or viral, infection has an increasesd chane of infecting host cells.

i. Epithelial hemidesmosomesi. A6B4

1. Targeted that results in blistering of the skin2. Mutation in either alpha or betaa subunit.

3. Autoimmune response3. Picture of adhesion and integrins

a. Blue = cytoplasmb. Alpha actininc. Ras pathway can Pi molecules that drive actin formationd. Focal adhesion

i. Sites that allow to adhere to EXC Matrixii. FAK – Focal Adhesion Kinase

1. Drives depolymerization of focal adhesions2. Drives depolymerization of actin and breakdown of Focal

Adhesions (FA)3. FA must first be made and then broken down

a. In order to be mobile, the cell must remove a FA and reform another at the point it adheres to the ECM

e. IRE – Integrin Receptor Kinasef. Hemidesmosomeg. Basal lamin has embedded EXM proteins, laminin is the most common’h. A6B4 is found in hemidesmosomes in epithelial cells

i. mechanical stress functions of the matrixi. Plectin

i. Associates with the ii. Plaqu

1. Made of plectin proteins2. Link with integrins

j. BPAG – bullbous phemphigoid antigen i. First identified in

ii.iii. Intermediate filaments are disrupted and iv. Immune system attacks BPAG antigoig

1. Immune cells recognize antigen and recognize it as a threat4. Tissue Organization

a. Simpleb. Stratifiedc. Columnard. Cuboidale. Squam

5. Basal Laminaa. E – epithelialb. Thin layer is basal laminac. Loose connective tissue, pictured belowd. 50nm in widthe. spans intermediate zone of whatever the tissue isf. separates epithelial cells from structural tissueg. creates permeable layerh. Functions of the Basal Lamina

i. Structural

ii. Permeability Barrieriii. Organization of cytoskeletoniv. Scaffolding function

1. Regeneration2. Cut skin3. Ulcer4. Tissue can heal, but only if basal lamina provides a scaffolding for

the divisioni. Picture

i. PMii. Integrins – green

iii. Many proteins bind to each otheriv. Perlecan links with type IV collagen and laminiv. Perlecan and nidogen do not link up

6. Cell Adhesiona. Three classes of adhesion

i. Occluding Junctions1. Sites hwere cells adhere to one another and inhibit the movement

of different molecules either across the CM or between the CMemebrane

2. Tight junctionsa. Apical side of cellsb.

ii. Adherin Junctions/Anchoring Junctions1. Hemidesmosomes

a. Link with intermediate filaments2. Desmosomes

a. “” on lateral side3. Adherin junctions

a.4. Link with components of cytskeleton

iii. Communicating Junctions1. Gap junctions

a. Act like shutters on a camerab. Driven by specific signalingc. Highly expressed in cardiac cells

7. Structures of junctionsa. Formation of the adherins junctionsb. Cadherins

i. Function when they bind to cadherins of ii. Homophilic binding

iii. E-cadherins1. Only these will link with another E-cadherin

a. Binding of Ca2+iv. N-cadherins

1. Neuronal cells

v. Require Ca2+ for binding1. Ca2+ binding sites are bound

a. Protein becomes more rigidi. More interaction

1. Form a dimer2. Allow PM to be brought the PM to be brought

together.3. Catenin is the linker protein that binds the

PM of the cadherins and links to vi. Actin filaments in belt like structure

c. Desmosomesi. Plaque proteins organize intermediate filaments

ii. Epithelial cells – keratiniii. Desomglein and desmocollin – have both EXC and Cytosolic sides