L38 Flashcards
What is extracellular matrix?
Spaces between cells composed of complex array of molecules
What are the roles of ECM?
Structural support and regulation of cell activities
Why do we organize ECM?
For function (eg Collagen)
What are ECM composed of?
Proteins (collagen, elastin, etc)
Proteoglycans
What are collagen rich in?
Proline and glycine repeats
What is the form of collagen?
An alpha chain, left handed
G-X-Y repeats
X = any aa (often proline or lysine)
Y = any aa (often hydroxy-proline or hydroxy-lysine)
The 3 levels of collagen :
Collagen forms -> collagen fibrils forms -> collagen fibres
Identify 3 types of collagens
Fibrillar collagens : type 1,2,3,5
Sheet-forming collagens : type 4
Fibril-associated collagens : 6,9,12
How are collagens synthesised
- Procollagens secreted into ER lumen
- add hydroxy group to proline or lysine
- exocytosed to extracellular space
- procollagen peptidase cleaves off propeptide sequence at N&C terminal
- collagen self-polymerises into fibrils
- Lysine cross-links to form collagen fibres
Why do we need propeptide sequence at N&C?
To prevent premature assembly of collagen molecule in cells
What affects tensile strength in collagen?
Extent of cross-linking
Identify the examples of collagen synthesis defects
Osteogenesis imperfecta - type 1 (failure to form triple helices-> brittle bones)
Achondrogenesis - type 2 (flexible joints)
Ehlers Danlos syndrome - type 3 (elastic skin)
Scurvy - cannot hydroxylate proline and lysines due to vit C deficiency
What is the characteristic of Adhesive ECM proteins?
Have multiple binding domains
Identify 4 ECM proteins that mediate adhesion
FLTC Fibronectin Laminin Tenascin Collagen
What is fibronectin important for?
Cell migration to reach cell differentiation
What is laminin important for?
Basement membrane formation
What are the functions of Proteoglycans?
- resist compressive forces by osmotic pressure
- regulate secreted-protein’ activity
What is the structure of proteoglycans?
Multiple (negatively-charged) GAG links to a core protein
Takes up 90% of space but dry weight is <10%
What does cell secrete
Organic components of ECM