Lecture slides and notes on ECM glycoproteins and proteoglycans. Includes notes on the extracellular matrix, the different glycoproteins and proteoglycans. Summarises their structure, and roles as well as brief section on chemokines
The Extracellular Matrix (ECM):
Some cells sit on prominent
layers of ECM –
basement membranes
Components include: -
- Fibrous glycoproteins – collagen, fibrin, elastin
- Large glycoproteins – fibronectin and laminin. Arent
necessarily fibrous
- Large proteoglycans – eg. perlucin
(Proteoglycans are polypeptides carrying glycosaminoglycans
-Long unbranched and highly negatively charged polysaccharide
chains
- Integrins are adhered to and combine components of ECM and
elements of the cytoskeleton. Provide a link between interior
cytoskeleton and ECM
Cells interact with the ECM via cell surface proteoglycans and
adhesion proteins eg. Integrins
Angiogenesis and Metastasis:
- Vascular cells are recruited to tumours
- Not all tumours undergo metastasis; once it
occurs, the cancer has spread around to
other cells
- Cancer cells release themselves from
adhesive interactions and enter the
lymphatic or circulatory system
- Cells escape from vessels (extravagate) and
go to tissues and proliferate
- Metastatic cancers; very few cells can do this
but only a few are needed to cause issues
, Fibronectin:
- Glycoprotein
- Has a big kD
- Bridged dimer
- Two regions arent identical due to splicing variants
- Collagen binding site, 3 fibrin ones, RDG motif (interact
with ECM and cell surfaces) and heparin sites
-
- Two polypeptides
- Large globular domain
- Two beta subunits contribute to short arms
- Bind to heparin; pair on short arms and one on
long domain
- Globular binding sites have binding for cell surface
glycolipids
- Interaction cross-links from ECM and cell surface
- Four classes
- All contain amino sugar
- Glucuronic acid has carboxyl group
- Hyaluronate is a good lubricant for cell surfaces
- Chondroitin sulphates; amino sugar is acetyl galactose
- abab repeat
- Multiple sulphate groups can attach to residue due to
inverse hanging groups
- No clear distinction between heparin and heparin sulphate
- When acetyl group leaves amino groups, they stay like that
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