Extracellular matrix

Question 1

Why is the extracellular matrix (ECM) important?

Answer 1

adhesion to other cells is critical to cell survival

Question 2

What cells can survive in suspension?

Answer 2

cancer cells are anchorage independent

Question 3

When does cell adhesion occur?

Answer 3

• whenever cells touch appropriate substrata

- it is selective

Question 4

What does the extracellular matrix (ECM) consist of?

Answer 4

• variety of proteins and polysaccharides that are secreted and assembled in close association with the cells that synthesize them
• serves as a scaffold for cells
• participates in regulating various cell functions (survival, differentiation, migration, proliferation, shape)

Question 5

What are the four major classes of molecules in the extracellular matrix?

Answer 5

• glycosaminoglycans (GAGs), usually linked to form proteoglycans
• fibrous proteins (collagen and elastin)
• multi domain adapter proteins, fibronectin and laminin
• water and many solutes

Question 6

What does proteoglycan molecules form?

Answer 6

a highly hydrated gel in which the fibrous and multi domain proteins are embedded

Question 7

What extracellular matrix has a distinct structure?

Answer 7

basal lamina

Question 8

What are the two characteristic components of the basal lamina?

Answer 8

collagen IV and laminin

Question 9

What do GAGs consist of?

Answer 9

unbranched polysaccharide chains composed of disaccharide repeats (amino sugar, e.g. N-acetyl-glucosamin, and uronic acid, e.g. glucuronic acid)

Question 10

Why do GAGs have a capacity to become highly hydrated?

Answer 10

their high negative charge

Question 11

What are proteoglycans?

Answer 11

covalently linked complexes of GAGs (one or many) and proteins

Question 12

Where are proteoglycans likely to play an important role?

Answer 12

• filtering function of the kidney glomerulus

- “reservoirs” of growth factors and proteases (they bind to them and may modify activity)

Question 13

What collagen is characteristic of the basal lamina?

Answer 13

Collagen IV

Question 14

What provides elasticity in tissues like the skin, lungs, blood vessels?

Answer 14

network of elastin in the ECM

Question 15

What are multi domain adapter proteins in the extracellular matrix and what do they do?

Answer 15

• proteins with multiple domains that act as binding sites for other matrix molecules and adhesion molecules on the surface of cells
• fibronectin, laminin, tenascin
• help organize the matrix and attach cells to it

Question 16

What does fibronectin do?

Answer 16

• assembles in the extracellular matrix into highly insoluble fibronectin fibrils
• has numerous binding sites for cells

Question 17

What does laminin do?

Answer 17

• found in basal lamina only

- have numerous binding sites for cells and other ECM proteins that link them to collagen IV

Question 18

What are matrix metalloproteases (MMP)?

Answer 18

• extracellular proteases that turn over the ECM

- important in tissue remodeling during development and in cell invasion of tissue

Question 19

What do advancing cells secrete to clear the migration path?

Answer 19

proteases

Question 20

What are functions of cell adhesion molecules (CAM)?

Answer 20

• adhesion and force generation against the ECM or other cells (form transmembrane link with the cytoskeleton)
• when bound to a ligand, CAMs signal their engagement via conformational change to the cell interior -> affecting cell function

Question 21

Cadherins

Answer 21

• binding is Ca2+ dependent
• bind to other cells via cadherins on the juxtaposed cell surface (homophilic binding) in a zipper like fashion
• common in intercellular junctional complexes

Question 22

Ig superfamily (IgSF) CAMs

Answer 22

• homophilic binding mechanism
• do not form dimers
• binding does not require Ca2+
• binding is mediated by multiple Ig domains

Question 23

Integrins

Answer 23

• binding is heterophilic
• composed of alpha/beta heterodimers (both participate in ligand binding)
• large variety of interns with distinct binding selectivities

Question 24

What must cell adhesion molecules (CAMs) be linked to?

Answer 24

the cytoskeleton

Question 25

How are CAMs linked to the cytoskeleton?

Answer 25

actin-binding proteins associated with the cytoplasmic tails of CAMs

Question 26

What are the associated proteins for cadherins?

Answer 26

cateneins

Question 27

What are CAM-associated proteins involved in?

Answer 27

- providing the cytoskeletal link - regulation of adhesion - in control of actin polymerization - cell signal mediated by CAMs

Question 28

Which cytoplasmic face of the membrane are CAMs paired with?

Answer 28

the face with complex protein assemblies that serve mechanical, controlling, and signaling functions

Question 29

Do adhesion sites play major roles in cell differential/development and cancer?

Answer 29

yes | - one of the early signs of carcinogenesis is a change in CAM