BS3540
Lecture 2: ECM glycoproteins & proteoglycans
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
Lecture 2: ECM glycoproteins & proteoglycans
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
