Cell Adhesion and the Extracellular Matrix Flashcards
What are GAGs?
Glycosaminoglycans
When organised by specific proteins, what do GAGs produce?
Glycosaminoglycans, when organised by special proteins, produce proteoglycans
What six types of cells are usually found in connective tissue?
1- Fibroblasts 2- Myofibroblasts 3- Chondroblasts 4- Osteoblasts 5- Adipocytes 6- Blood cells
What are the two main components of ECM?
1- Fibrillar proteins
2- Polysaccharide glycosaminoglycans (GAGs) which form proteoglycans
What are four examples of fibrillar proteins?
1- Collagen
2- Elastin
3- Fibronectin
4- Laminin
What is the role of fibroblasts?
Synthesise collagen, elastin and proteoglycans
Where is collagen synthesised?
RER of fibroblast
What is the precursor to collagen?
Precollagen then tropocollagen
What does collagen need to form a triple helix?
1- Vitamin C
2- Supplied -OH in order to allow for triple helix to form
How is precollagen made into tropocollagen?
Precollagen is released into the ECM and cleaved to form tropocollagen. Extremely insoluble.
What is the solubility of tropocollagen?
Extremely insoluble
How is tropocollagen made into collagen?
Aggregation of tropocollagen via enzyme-catalysed cross-linking, making a fibril
Describe the process of collagen secretion.
1- Collagen is packaged into large, specialised vesicles in the RER
2- Collagen secretion occurs by exocytosis at specialised sites
3- Collagen is organised and collagen fibrin is produced in a membrane tube called fibripositor
In regards to surrounding tendons, how are fibroblasts oriented?
They are oriented along tendon direction in groups so that collagen produced is correctly oriented (parallelism of tendon)
Where is elastin produced?
1- Fibroblasts
2- Smooth muscle cells
3- Chondroblasts
Where is elastin usually found?
In places it needs to stretch, e.g. aorta, as it has a tendency to stretch and recoil
What are proteoglycans an assemblage of?
GAGs and proteins
What are the roles of proteoglycans?
1- Matrix support, cushioning and hydration
2- Glue-like function for adhesion
3- Links between ECM proteins, ECM and cell surgace
Describe the structure of GAGs.
1- Long chains of repeating disaccharide units
2- Highly negatively charged
3- Highly hydrated
What is hyalyuronic acid?
A repeating dissacharide in GAG
How is ECM linked to cytoskeleton?
1- Collagen or proteoglycan
2- These bind fibroconectin, which links to integrins, which in turn bind via adatorss to the actin cytoskeleton
What are the roles of myofibroblasts?
1- Secrete collagen (fibroblast-like)
2- Synthesise actin, myosin and desmin (smooth-muscle like)
What do granules in mast cells contain?
1- Heparin
2- Histamine
How are myofibroblasts involved in tissue damage?
1- Prolerate
2- Secrete collagen which helps form a scaffold
3- Consolidate damaged area by forming a fibrous scar
4- Contract to reduce the size of damaged area, thus expressing focal adhesions and smooth muscle actin
What is the main role of plasma cells?
Producing antibodies through the secretory pathway
What is the main role of macrophages?
Ingesting Listeria bacteria/paramecium
What are the main roles of adipocytes?
1- Insulation
2- Packing
3- Storing energy
What is the ob gene?
1- Mutant gene
2- Leads to excessive eating
3- Obesity is induced
4- ‘Deleted’ by leptin
What provides the satiety signal?
Leptin
What happens to leptin levels in obese patients?
Increases due to decreased sensitivity/increased resistance
What are the roles of tight junctions?
1- Define polarity
2- Control passage of substances between cells
3- Link to actin cytoskeleton
What is the role of tight junctions?
Plaque anchors actin filaments at the membrane
What are the four main types of cadherins?
1- E-cadherin
2- N-cadherin
3- P-cadherin
4- VE-cadherin
Where are E-cadherins usually found
Epithelia
Where are N-cadherins usually found?
1- Neurons
2- Heart muscle
Where are P-cadherins usually found?
1- Placenta
2- Epidermis
Where are VE-cadherins usually found?
Endothelial cells
What is the role of desmosomes?
Linking between strong intermediate filaments and adjacent cells
What are the two main structural components of desmosomes?
1- Plaque
2- Filaments
What are the roles of gap junctions?
1- Communication
2- Hydrophobic channel
3- Allow passage of small molecules
4- Coordinate function
What are the roles of focal adhesions?
1- Link ECM with cell cytoskeleton
2- Ac as signalling platforms
3- Link to fibronectin
How do focal adhesions link the ECM with cell cytoskeletons?
Link ECM through integrins with actin filaments of the cytoskeleton
What are the roles of hemidesmosomes?
1- Link ECM to cell cytoskeleton
2- Link to laminin in basement membrane
How do hemidesmosomes link the ECM with cell cytoskeletons?
Link ECM though integrins to intermediate filaments of cytoskeleton
What are integrins?
Large family of proteins which bridge between the cell cytosol and ECM
Give two examples of integrins.
1- Fibronectin
2- Laminin
What is Duchenne’s Muscular Dystrophy?
1- A gene mutation which leads to the absence of dystrophin (adaptor) due to the premature termination of translation 2- Leads to damage to muscle fibre 3- Muscle wasting 4- Muscle weakness 5- Unable to walk by 12 years of age
What is the cause of Duchenne’s Muscular Dystrophy?
Gene mutation which leads to the absence of dystrophin (adaptor) due to the premature termination of translation
What is PTC 124?
1- Also called ataluren
2- Experimental druh
3- May override premature stop signal mutation and lead to normal production of dystrophin
What are the three steps of cell adhesion in cancer stages?
1- Carcinoma in situ
2- Microinvasion
3- Progression to metastasis
Define carcinoma in situ.
1- Tumour cells accumulate to cells’ mutations disregulating the normal cell cycle
2- Cells have yet not breached basement membrane
What happens during microinvasion?
1- Expression of cadherins is reduced, leading to the cells converting to ‘mesenchymal’ cells
2- Microinvasion begins and is aided by the secretion of metalloproteases
3- Basement membrane is breached
4- In invading tumours, cells express integrin to promote interaction with ECM and non-epithelial cells during movement
What happens in progression to metastasis?
1- Autocrine motility factors are secreted thus increasing motility
2- Angiogenesis factors such as VEGFs are secreted thus promoting vascularisation
3- Metastising tumour enters into lymphatic and blood circulations
4- Invasive carcinoma
