Lecture 22 - The vertebrate ECM Flashcards
What are the 3 classes of macromolecules of the vertebrate ECM?
Fibrillar glycoproteins (collagen, elastin)
Adhesive glycoproteins (fibronectin, laminin)
Matrix proteoglycans and glycosaminoglycans
What are the steps that a cell takes to migrate?
1) Protrusion of lamellipod.This is done via actin polymerisation.
2) Focal adhesion mediated by integrin receptors which are linked to actin filaments.
3) Contraction of myosin found on actin filaments to bring the cell body forward.
4) Process repeats
* Cell membrane rotates during this process.
What is the function of GAGs and proteoglycans?
glycosamino glycans and proteoglycans are major matrix compoenents of the ECM;
They form porous hydrated gels
Fill most of the extracellular space
They also provide mechanical support.
What are some examples of GAG polysaccharies and proteoglycans?
Hyaluronan is a high molecular weight GAG polysaccharide
Large modular proteoglycans which are heavily modified with GAG chains which contain hyaluronan.
Cell surface and secreted heparan suplphate - proteoglycans.
What are some features of GAGs?
Unbranched polysaccharides
Repeating disaccharide units
One sugar is an amino sugar
Other sugar is glucuronic acid
Highly charged molecules
Adopt extended conformation.
What is the function of hyaluronan?
hyaluronan sits in ECM space and gives a gel-like texture to surrounding fluid.
What is the function of large proteoglycan aggregates?
aggrecan aggreggate is an example of a large proteglycan aggregate
it is involved in forming hydrated gels (like hydraluronan)
These aggregates are branches of hydraluronan.
How does heparan sulfate regulate binding of FGF to their receptors on the cell surface?
Heparan sulfate branches of matrix proteoglycans can bind FGF receptors. When cell damage occurs the heparan sulfate separates from the central proteoglycan and allows the FGF receptor to bind to the growth receptors which results in a response to the damage.
Proteolysis of the heparan sulfate is the process that results in its suspension in the ECM matrix.
How does syndecan use the heparan sulfate that it is bound to?
syndecan can also bind heparan sulfate and can allow binding of FGF to their receptors in an autocrine manner.
What kind of binding occurs between cadherin molecules?
Homotypic binding occurs between cadherins on the plasma membrane of opposing cells.
What are the types of cell-cell adhesion that can take place?
Homophillic/homotypic binding involves interaction via identical molecules and heterophillic binding involves interaction between different molecules.
What is required for their function? What is the function of cadherins?
Calcium is required for adhesion of cadherins.
Expressed in high levels in solid tissues
Mediate the major tissue specific cell-cell adhesion interactions
Maintain ordered selective cell-cell adhesion (prevent different cell types from mixing)
Continued expression is required for the maintenance of tissue structure.
Play a crucial role in morphogenesis and tissue development.
How many different cadherins are there?
more than 100 different types;
E-cadherins are between epithelial tissue.
N-cadherins between nerves/mucles
P-cadherins in the placenta
What is the structure of cadherins and their interaction like?
interaction between cadherins is at the N-terminal domain which includes various binding sites.
Cadherin polypeptide has a single transmembrane domain.
Polypeptide has 5-6 cadherin domain repeats.
distance between cells is about 39 nm
What is the function of calcium in cadherin function?
Calcium is necessary for the extension of the cadherin molecules making them essential for cell-cell binding.
> 1mM Ca=extended conformation
