Extracellular Matrix

Front 1

What are the two components of extracellular matrix?

Back 1

Fibers (collagen and elastin)
Ground substance (GAGs-proteoglycans associated with protein core)

Front 2

What are the three supporting tissues in connective tissue?

Back 2

basement membranes, cartliage, bone

Front 3

Is basal lamina considered connective tissue?

Back 3

Yes

Front 4

What is the basement membrane? Where are they found?

Back 4

They are found everywhere, they are thin sheets of extracellular matrix that underlie all epithelium, nerve, etc.
Composed of lamina lucida, lamina densa, and lamina reticularis

Front 5

What are the two parts of the basal lamina? why is the third lamina not part of this basal lamina?

Back 5

Lamina lucida and densa:: depends on where they are synthesized. Lamina lucida and densa are synthesized by the overlaying epithelial cells, reticularis are synthesized by cells in underlying connective tissue

Front 6

What are the five molecules that we need to know regarding the basement membranes?

Back 6

Collagen type IV, heparan sulfate proteoglycan, lamini, entactin, fibronectin

Front 7

Which of the three in the basement membrane is impossible to determine where it ends on an EM?

Back 7

Lamina reticularlis:impossible to determine where the reticularis ends and the underlying connective tissue begins

Front 8

Lamina lucida: what is the primary molecule? Explain it's shape.

Back 8

Laminin::asymmetrical cross shaped molecule that has numerous globular domains on each of its arm (long arm has one unit)

Front 9

What is laminin composed of? What are the long arms made of?

Back 9

alpha, beta, and gamma peptides.
Long arms made of alpha helices that form coiled coil

Front 10

Alpha chain of laminin: what binding site does it have?

Back 10

Heparan sulfate binding site (on its single unit side) binds to sugar

Front 11

Gamma chain of laminin: what are the binding sites there?

Back 11

Short arm: proteoglycan binding site, entactin attachment site ON the short arm

Integrin (cell surface receptor) binding site on long arm (endocrine binding site)

Front 12

Beta chain of laminin: what are the binding sites there?

Back 12

short arm: heparan sulfate binding site and proteoglycan binding site
long arm: integrin binding site

Front 13

Laminin can also bind to what else and form what?

Back 13

It can bind to itself and form a network: primary component of lamina rara/lucida

Front 14

Lamina densa: what is it primarily composed of? Describe it. What kind of interactions are there for the domains? Parallel or antiparallel? What kind of shape does the type 4 collagen network look like?

Back 14

Composed of type 4 collagen
Triple helical collagenous domain in the middle (red)--composed of 3 peptides
2 noncollagenous domains: C terminal NC1, N terminal doman 7S)

Noncollagenous domains allow interaction between type four collagens (head to head fashion via 7S or NC domains)

Collagen interact in an ANTIPARALLEL fashion

Forms sheet (stabilized by these interactions) form a multilayered network

Front 15

Laminin in the gamma chain has a binding site for entactin. Explain entactin

Back 15

Entactin's function: bind lamina rara and densa
Binding sites for collagen of densa and laminin of lamina rara

Front 16

Epithelial cells interact with basal lamina via ______

Back 16

Integrins (beta and gamma peptides of laminin in lamina rara)

Front 17

Integrins cross plasma membrane and interact with cell via attachment proteins. What are some examples? What do they interact with in the cell?

Back 17

Talin, Vinculin, alpha actinin, etc.
Interact w/ the ACTIN CYTOSKELETON of the cell

Front 18

What is junctional epidermolysis bullosa?

Back 18

Mutations in integrins or laminin chains result in detachment of epithelium from basement membrane

Skin::epithelium is sloughing off of the underlying dermis

Front 19

Fibronectin. Talk about it. what are the 2 domains? How is the dimer formed?

Back 19

Fibronectin is a dimer that is formed by disulfide bonds at the C-terminal end.
2 domains: cell binding domains and a collagen binding domains

Permits interactions between cells and an extracellular matrix molecule

Cells don't always refer to epithelial cell (can be cell surface receptors of resident or transient cells)

Front 20

What are transient cells?

Back 20

Cells of the immune system

Front 21

Are fibroblasts resident cells or transient cells?

Back 21

Resident cells

Front 22

Proteoglycans. Talk about it. What is attached to them? What do they sequester? How? How come receptors do not interact with what is sequestered?

Back 22

Core protein to which GAG side chains attach. Heparan sulfate GAG side chains and chondroiton sulfate GAG side chains.

Sulfate groups:: highly negatively charged (and extremely long--2sugars repeated hundreds of times)::function--sequester GROWTH FACTORS (suppositories...basement membranes are considered repositories of GFs)

No interaction with Growth factors by GF receptors because they are bound up by the GAG side chains

Front 23

Where is lamina reticularis synthesized?

Back 23

Underlying connective tissue

Front 24

What types of fibers are abundance in LF (lamina reticularis)?

Back 24

Type 3 collagen::reticular fibers

Front 25

The glomerular basement membrane in kidney is a specialized basement membrane, with podocytes up top and endothelial cells that line the capillaries of the glomerulus in the kidney. What is this membrane like? What is missing?

Back 25

Fusion of two basal laminas: one synthesized by podocytes and one syntehsized by the endothelial cells. Fuse to form a subendothelial lamina rara and a subepithelial lamina rara and an extra thick lamina densa

Missing lamina reticularis, but it is still called a basement membrane

Front 26

In diabetic patients, what happens to the kidney? Can they be seen in the ECM?

Back 26

Basement membranes are thickened
No they can't be seen in the ECM, they are seen in the basement membrane

Front 27

Why is PAS staining used?

Back 27

Cannot see with H&E stain
PAS: stains carb/sugars of the basement membrane

Front 28

What is AGE? How is it formed?

Back 28

advanced glycated end-products

results from inability to process glucose::excess glucose in blood, and it gets broken down and interacts with amino acids

Reactive oxygen intermediates are formed, which are highly reactive, and then they react with proteins in circulation or basement membrane (or throughout connective tissue)

These bind to and PERMANENTLY alter proteins, and these are called AGE

Front 29

What happens with AGE? what can it bind to? What happens then? Which is naturally occurring?

Back 29

Because they are much more stable than naturally occurring proteins, they are more difficult to degrade in the normal process of turning over proteins::contribute to a thicker membrane

They can also bind to RAGE (receptor for AGE) and result in a signaling pathway being activated that CHANGES GENE EXPRESSION within a cell and alters it to do a number of things, including PRODUCING MORE BASEMENT MEMBRANE.

RAGE is naturally occurring, but not AGE