Extracellular matrix Flashcards
Why is the extracellular matrix (ECM) important?
adhesion to other cells is critical to cell survival
What cells can survive in suspension?
cancer cells are anchorage independent
When does cell adhesion occur?
- whenever cells touch appropriate substrata
- it is selective
What does the extracellular matrix (ECM) consist of?
- 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)
What are the four major classes of molecules in the extracellular matrix?
- glycosaminoglycans (GAGs), usually linked to form proteoglycans
- fibrous proteins (collagen and elastin)
- multi domain adapter proteins, fibronectin and laminin
- water and many solutes
What does proteoglycan molecules form?
a highly hydrated gel in which the fibrous and multi domain proteins are embedded
What extracellular matrix has a distinct structure?
basal lamina
What are the two characteristic components of the basal lamina?
collagen IV and laminin
What do GAGs consist of?
unbranched polysaccharide chains composed of disaccharide repeats (amino sugar, e.g. N-acetyl-glucosamin, and uronic acid, e.g. glucuronic acid)
Why do GAGs have a capacity to become highly hydrated?
their high negative charge
What are proteoglycans?
covalently linked complexes of GAGs (one or many) and proteins
Where are proteoglycans likely to play an important role?
- filtering function of the kidney glomerulus
- “reservoirs” of growth factors and proteases (they bind to them and may modify activity)
What collagen is characteristic of the basal lamina?
Collagen IV
What provides elasticity in tissues like the skin, lungs, blood vessels?
network of elastin in the ECM
What are multi domain adapter proteins in the extracellular matrix and what do they do?
- 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
What does fibronectin do?
- assembles in the extracellular matrix into highly insoluble fibronectin fibrils
- has numerous binding sites for cells
What does laminin do?
- found in basal lamina only
- have numerous binding sites for cells and other ECM proteins that link them to collagen IV
What are matrix metalloproteases (MMP)?
- extracellular proteases that turn over the ECM
- important in tissue remodeling during development and in cell invasion of tissue
What do advancing cells secrete to clear the migration path?
proteases
What are functions of cell adhesion molecules (CAM)?
- 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
Cadherins
- 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
Ig superfamily (IgSF) CAMs
- homophilic binding mechanism
- do not form dimers
- binding does not require Ca2+
- binding is mediated by multiple Ig domains
Integrins
- binding is heterophilic
- composed of alpha/beta heterodimers (both participate in ligand binding)
- large variety of interns with distinct binding selectivities
What must cell adhesion molecules (CAMs) be linked to?
the cytoskeleton
How are CAMs linked to the cytoskeleton?
actin-binding proteins associated with the cytoplasmic tails of CAMs
What are the associated proteins for cadherins?
cateneins
What are CAM-associated proteins involved in?
- providing the cytoskeletal link
- regulation of adhesion
- in control of actin polymerization
- cell signal mediated by CAMs
Which cytoplasmic face of the membrane are CAMs paired with?
the face with complex protein assemblies that serve mechanical, controlling, and signaling functions
Do adhesion sites play major roles in cell differential/development and cancer?
yes
- one of the early signs of carcinogenesis is a change in CAM
