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In connective tissue, the main stress-bearing component is the ___.
In epithelial tissue, the ___ form the main stress-bearing component.
cytoskeletons of the cells themselves (linked by anchoring junctions)
What is the purpose of the ECM?
- Provides scaffolding and support for tissues and cells.
- Signal transduction.
What makes up the ECM?
proteoglycans, collagen, laminim, fibronectin, and vitronectin.
"filler" substance. Traps water. Binds cations.
Most abundant ECM component. Connective tissue.
Forms network of weblike structures that resist tensile forces.
Glycoproteins. Maintains cell shape.
Glycoprotein. Promotes cell adhesion and spreading.
What are two principles of tissue formation?
- Cells must be attached to each other.
- Cells must be attached to a scaffold.
Why must cells be attached to each other?
Protein-protein interaction between cells.
Why are cells attached to a scaffold?
- Cells secrete proteins and carbs which make up the ECM.
- Intermembrane proteins connect the ECM with the cell's cytoskeleton.
What types of proteins are used in cell adhesion?
Cadherins, selectins, integrins, Ig family
Tissue specific; dimerize; Ca+2 dependent; regulate cell shape and migration.
Cancer cells also change ___ expression.
Cadherins affect cell shape and migration via ___.
- Cell adhesion molecules that bind to sugars.
- Type of lectin.
In wound-clotting, what is selectin-dependent?
Weak adhesion and rolling.
In wound-clotting, what is integrin-dependent?
- strong adhesion and emigration
- Lets white blood cells exit capillary
What are three kinds of cell junctions?
Describe adhesive junctions.
- Desmosomes and adherens.
- Hold cells together in fixed positions w/in tissues.
- Ca+2 dependent.
What are two types of adhesive junctions?
Desmosomes and adherens (both Ca+2 dependent)
Describe the structure of desmosomes.
- Keratin intermediate filaments connected to plaque.
- Plaque composed of anchor proteins.
- Transmembrane cadherin adhesion proteins attached to plaque.
What makes up the transmembrane cadherin adhesion proteins?
desmoglein and desmocollin.
What proteins make up the plaque?
What is the purpose of the intermediate filaments attached to the plaque?
structural support (not movement)
Describe tight junctions.
- Seal space between cells.
- Prevent flow of molecules and ions thru EC space.
- Important for organs that store liquids.
What proteins make up tight junctions?
claudin and occluding
Describe gap junctions.
- Most common type of junction between animal cells.
- Form open channels between cells allowing ions and small molecules to pass.
- Useful for cell-cell communication.
- Open at low Ca+2 and low pH
What binds to gap junction to open the channel?
calmodulin (also binds to calcium)
What kind of molecule can pass thru a gap junction?
small (e.g. cAMP)
How is the ECM formed?
Secreted by the cells
- Used in cell-cell adhesion.
- Serve as attachment to ECM.
- Bind to specific ECM proteins.
Describe how collagen fibers are formed.
- Procollagen triple-helix formed in ER/Golgi complex.
- Single procollagen molecule out via secretory vessicle.
- Cleavage of propeptides.
- Thousands of collagen molecules form fibril in ECM.
- Aggregation of fibrils form collagen fiber.
What is the purpose of proteoglycans?
- Trap water and provide elasticity (e.g. skin).
- "Filler" substance.
- Hold ECM in place.
Describe structure of proteoglycans.
- 95% carbs by weight.
- glycosaminoglycan (GAG) is main component.
- Single polypeptide with hundreds of GAGs.
What holds the ECM in place?
Linkages of proteoglycans to cell membranes.
What are three types of interactions for proteoglycans?
- Binding to ECM.
- Integrins binding to proteins in ECM.
What are two adhesive glycoproteins?
fibronectin and laminin
What's the main purpose of Fibronectin?
Provides/maintains cell shape.
Describe fibronectin structure.
- Two large polypeptides (not identical) linked by disulfide bridges.
- Some domains bind to ECM.
- Other domains bind to membrane receptors.
How is fibronectin specificity determined?
By the a.a.'s flanking the RGD motif
What are integrins?
- Receptors that mediate attachment between cells and ECM/other cells.
- Critical for growth, hemostasis, and host defense.
- Interact with cytoskelton.
Describe integrin structure.
- Heterodimeric with alpha and beta subunits.
- Variable subunits - mammals have 18 alpha, 8 beta
- e.g. melanoma: alpha-v, beta-3
Describe the integrin receptor.
- Binds to soluble and attached ligands.
- Binding changes conformation of the dimer.
- Binding is Mn+2 dependent.
- Clustering occurs with other integrin receptors upon ligand binding.
What are the two types of integrin activation?
- Outside-in - info from outside to cell
- Inside-out - info from cell to outside
Integrins can bind to the ___, with a ___ of integrins.
same target, cluster
What is anoikis?
Cells cease to be bound to ECM leading to cell death
What are the typical results of integrin signalling?
Cell death, cell migration, cell shape change, cell division
What does integrin clustering do in normal cells?
Affects cell migration and differentiation.
What does integrin clustering do in cancer cells?
Angiogenesis and metastasis
How does integrin clustering affect FAK and MAPK pathways?
- Focal adhestion tyrosine kinase -> cell survival
- MAP Kinase -> differentiation, cell growth, apoptosis