Cell interactions with ECM Flashcards
- Know that elastin forms elastic networks that are stabilized by specialized crosslinks derived from aldehydes of lysine and the action of lysyl oxidase.
- Elastin crosslinks, or desmosines, derive from lysine and the aldehydes of lysine produced by lysyl oxidase
- 4 different polypeptides of elastin can become part of elastic tissue
Learn that fibronectin is a collagen binding, cell binding, proteoglycan binding component, and that these functions are accomplished by distinct protein domains.
Fibronectin is a CT glycoprotein that is often used as an example of the functions of ECM
-Fibronectin biological properites include collagen binding and cell binding are in discrete domains. Cell binding domain is expanded
Recognize that different fibronectin forms are made from one gene by alternate splicing of fibronectin messenger RNA. Alternate splicing is a common means to regulate function of genes in humans.
- self association, collagen binding, cell binding and heparin binding
- RGD (Arg, Gly, Asp) recognize on ECM proteins that cells like to attach to
Identify laminin structure, and how it is performs analogous function to fibronectin in basal lamina.
- Laminin has the following chains: a chain, B chain, y chain; along with globular domains and an coiled coil a-helical domain
- Laminin serves functions in the basement membrane similar to fibronectin in other tissues
- Number of sheets of Type IV collagen that laminin binds is directly proportional to will enable greater strength
Describe components in a basal lamina, and how they assemble to form this specialized connective tissue.
-Often in this order=> epithelium, basal lamina, collagen
- Describe the general structure and location of integrins, and their role in assisting cell adhesion to extracellular matrix.
- Why does fibronectin and actin found together?
- integrins=> transmembrane proteins that bind ECM and intracellular cytoskeleton and signalling molecules
- integrin binds to fibronectin in the ECM and to actin in the Intracellular membrane through an adaptor protein.
Describe the Integrin structure
- 2 transmembrane polypeptides; a and B subunit
- ECM portion binds matrix proteins and communicate information to the cell
- intracellular portion binds to intracellular cytoskeletal and signalling machinery
- cytosolic tails can bind to actin
Describe Integrin activation
ECM protein is present when a extracellular signal binds to a plasma membrane receptor
PM receptor sends intracellular signal to integrin to activate it
Once activated, the integrin will bind to the ECM protein through a fibronectin
Understand how type IV collagen forms a network instead of a fiber to provide the scaffolding for basal lamina.
- Type IV collagen forms a sievelike network, which are overlaid on one another to tailor-make sieves for each function
- Type IV binds to laminin (an integrin binding adaptor like fibronectin) in other tissues
- Basal lamina starts with a Type IV collagen scaffold
Recognize the role of basal lamina as a barrier to cells, macromolecules, and solutes.
Basal lamina separates types of ECM and cells and can be found in muscle, epithelium, kidney…etc
-Basal lamina structure is a solute and cell barrier
T/F normal differentiated cells only maintain themselves when surrounded by familiar and expected extracellular matrix, eg. Bone cells die in a chondrocyte matrix, etc.
true
Remember, successful metastatic tumor cells learn to adjust to unfamiliar surroundings to metastasize where they do not belong. To accomplish this they use normal tools of cells and extracellular matrix in an abnormal way. Describe this:
invasive cells must break through basal lamina barrier (MMPs)
be able to move (integrins matched to 1st new ECM
go through 2nd basal lamina and survive in blood/lymph
able to move and survive 2nd new ECM to metastasize
What is the role of the specific tissue? cartilage, tendon, artery, bone, basal lamina
- Cartilage-resist compression, shock absorber
- Tendon-strength for pulling
- Artery-radial elasticity
- Bone-support weight bearing
- Basal lamina-cell and molecular barrier
What structure in elastin is caused by high amounts of hydrophobic amino acids which excludes water?
-beta spiral
What does squeezing out the water allow elastin to do when its shape is stretched?
-bounce back
