Cell Adhesion 4 - Adhesion on behaviour Flashcards
What is compaction?
- hallmark event of 8 cell stage in mouse embryo developement
- when you can no longer see the intercellular boundaries as adhering junctions form
- E-cadherin is essential for formation of adhering here
- found mainly on basolateral cell-cell contact sites
Where is E-cadherin mainly found during compaction?
Basolateral cell-cell contact sites
Describe 2 experiments defining cadherin-mediated adhesion
- adhesion-blocking antibodies - exposure to anti-cadherin antibodies causes embryo to fall apart
- expression and deletion of cadherin - mutant embryos lacking E-cadherin fall apart
Explain loss and gain of function mutations
- if you remove what you think is causing the effect, does the effect still happen?
- when the feature is back does it function again?
name 3 different types of cadherins?
- E-cadherin
- R-cadherin
- Cadherin-6
Where is E-cadherin expressed in the embryo?
- mainly in epithelial cells
Where is R-cadherin and N-cadherin mainly expressed?
nerve, muscle and lens cells
Where is P-cadherin expressed in the embryo?
- placenta
- epidermis
Where is Cadherin-6 expressed?
kidney
What is homopihilic binding?
- 2 molecules that are identical on different cells bind
What is heterophilic binding?
two molecules that are different on different cells bind
Explain homophobic binding in cadherin
- happens at the N-terminus - furthest point from the membrane
- Ca2+ is required or hinge would be floppy
- Changes conformation of the N-terminus
Explain overall connections of cadherins
- individual interactions are relatively weak
- combination is strong
- important as cell-cell interactions commonly break and re-from during embryonic development
What allows cells to sort according to origin
- homophilic binding - cadherins bind well to the same type of cells
- suggests that tissues are maintained by differential affinities of cells for each other
What causes tissue maintenance
- cadherins bind well to the same type of cell
- cells have differential affinities for each other
What is an L-cell?
cells in the GI tracts that secreted hormones regulating appetite
Explain L-cells and cadherins
- they do not normally express cadherins
- can be cultured to express L-cells
What does a higher level of catherine expression mean?
- stronger interaction - more tightly packed in the centre
What does a lower level of expression of cadherin mean?
- weaker interactions - around the outskirts
Explain overall sorting of cells based on their catherine expression
- express different cadherins - will group together into completely different groups
- express different levels of the same cadherin
- more cadherin in the centre, less catherine in outskirts
Explain the expression of cadherins in neural tube development
- ectoderm expressed E-cadherin
- as neural tube starts to form - stop making E-cadherin - start making N-cadherin
- cadherin 6B expressed increases at join between E-cadherin and N-cadherin
- some cells stop making N-cadherin and start making cadherin-7
- neural crest is then formed and more cadherin-7 is made
DRAW IT OUT
What is the effect of over expression of N-cadherin in neural tube formation?
- failure to leave the neural tube
Name 6 epithelial features
- regular columnar morphology
- high degree of cell adhesion
- cell-cell junctions
- specialised apical membrane (eg brush border)
- underlying basement membrane
- cells relatively static
Name 6 mesenchymal features
- irregular rounded or elongate morphology
- loss of apico-basal polarity
- front-back polarity
- dynamic adhesions
- lamellipodia and filopodia
- cells highly motile
What are lamellipodia?
- protrusion from migrating cells
- lots of actin
what are filopodia?
- extensions in migrating cells
- made of membrane
- sensory function
Explain the epithelial-mesenchymal transition (EMT)
- formation of epithelium is reversible
- cells can transition from epithelium so mesenchymal cells
Explain epithelial-mesenchymal transition in cancer progression
- cancer happens due to an accumulation of mutations in different genes
- allows for metastasis
- carcinomas are around 80% of all cancer cases
- metastasis accounts fro 90% of cancer deaths
What is carcinoma?
- cancers arising from epithelial cells
What are selections?
- proteins on the cell surface that bind carbohydrates
- expressed by white blood cells and epithelial cells (these line the blood vessels)
- linked to actin through transmembrane proteins
- mediate cell-cell adhesions in the bloodstream
Explain the role of selectins in inflammation
- weak binding and rolling of white blood cells along blood vessels
- leukocytes activate integrins, which recognise epithelial membrane proteins
- stronger adhesion
- lymphocyte will escape into the tissues
Explain defects in leukocyte adhesion
LAD-I - absent or decreased integrins - defective tight adhesion and invasion
LAD-II - glycosylation defect causing selectin defects - defective initial binding and rolling
LAD-III - activation defect of integrin - defective tight adhesion and invasion
What does LAD stand for?
leukocyte adhesion deficiency
What is LAD-I?
absent or decreased integrins - defective tight adhesion and invasion
What is LAD-II?
glycosylation defect causing selectin defects - defective initial binding and rolling
What is LAD-III?
activation defect of integrin - defective tight adhesion and invasion
What is the role of remodelling of the ECM in inflammation?
allows white blood cells tp pass between cells
Name the 2 main groups of ECM degrading enzymes
- matrix metalloproteinases (MMPs) -> need Ca2+ or Zn2+ to work
- serine proteases -> conserved serine residue on the active site
Very specific enzymes
Explain localised ECM degradation
- overall ECM structure stays the same
- but there is enough room for cells to migrate through
Explain localisation of ECM degradation
- some proteases secreted in inactive forms
- localised activator converts to be active
- tissue plasminogen activator activates plasminogen to dissolve blood clots
- some proteases confined by cell-surface receptors
- urokinase-type plasminogen activator (uPA) found at the growing tip of migrating cells
- some proteases are inhibited by locally secreted inhibitors
- tissue inhibitors of metalloproteinases (TIMPs)
Explain ECM remodelling in cancer
- carcinoma in situ
- basement membrane breakage
- proteolytic ECM degradation happens
- invasive tumor
- tumor spreads
