Extracellular matrix Flashcards

1
Q

Why is the extracellular matrix (ECM) important?

A

adhesion to other cells is critical to cell survival

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2
Q

What cells can survive in suspension?

A

cancer cells are anchorage independent

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3
Q

When does cell adhesion occur?

A
  • whenever cells touch appropriate substrata

- it is selective

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4
Q

What does the extracellular matrix (ECM) consist of?

A
  • 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)
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5
Q

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

A
  • glycosaminoglycans (GAGs), usually linked to form proteoglycans
  • fibrous proteins (collagen and elastin)
  • multi domain adapter proteins, fibronectin and laminin
  • water and many solutes
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6
Q

What does proteoglycan molecules form?

A

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

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7
Q

What extracellular matrix has a distinct structure?

A

basal lamina

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8
Q

What are the two characteristic components of the basal lamina?

A

collagen IV and laminin

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9
Q

What do GAGs consist of?

A

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

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10
Q

Why do GAGs have a capacity to become highly hydrated?

A

their high negative charge

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11
Q

What are proteoglycans?

A

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

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12
Q

Where are proteoglycans likely to play an important role?

A
  • filtering function of the kidney glomerulus

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

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13
Q

What collagen is characteristic of the basal lamina?

A

Collagen IV

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14
Q

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

A

network of elastin in the ECM

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15
Q

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

A
  • 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
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16
Q

What does fibronectin do?

A
  • assembles in the extracellular matrix into highly insoluble fibronectin fibrils
  • has numerous binding sites for cells
17
Q

What does laminin do?

A
  • found in basal lamina only

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

18
Q

What are matrix metalloproteases (MMP)?

A
  • extracellular proteases that turn over the ECM

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

19
Q

What do advancing cells secrete to clear the migration path?

A

proteases

20
Q

What are functions of cell adhesion molecules (CAM)?

A
  • 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
21
Q

Cadherins

A
  • 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
22
Q

Ig superfamily (IgSF) CAMs

A
  • homophilic binding mechanism
  • do not form dimers
  • binding does not require Ca2+
  • binding is mediated by multiple Ig domains
23
Q

Integrins

A
  • binding is heterophilic
  • composed of alpha/beta heterodimers (both participate in ligand binding)
  • large variety of interns with distinct binding selectivities
24
Q

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

A

the cytoskeleton

25
Q

How are CAMs linked to the cytoskeleton?

A

actin-binding proteins associated with the cytoplasmic tails of CAMs

26
Q

What are the associated proteins for cadherins?

A

cateneins

27
Q

What are CAM-associated proteins involved in?

A
  • providing the cytoskeletal link
  • regulation of adhesion
  • in control of actin polymerization
  • cell signal mediated by CAMs
28
Q

Which cytoplasmic face of the membrane are CAMs paired with?

A

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

29
Q

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

A

yes

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