Cell adhesion Ii - The social life of cells Flashcards
What are adherens junctions?
Mediate cell-cell adhesion
Anchor actin microfilaments to the membrane
What are adherens junctions composed of?
Classical cadherins - E cadherin
Beta catenin or Plakoglobin
Alpha catenin
What are the main classical cadherins?
E-cadherin (epithelial)
N-cadherin (neuronal)
P-cadherin (placental)
VE-cadherin (vascularised epithelial)
What are classical cadherins?
Single pass transmembrane glycoproteins
ECM consists of 5 cadherin repeat domains
Adhesion is Ca dependent
Cadherins are arranged in parallel in AJs
What is the cadherin superfamily?
Classical - Interact with cytoplasmic proteins and are linked to actin microfilaments
Desmosomal - Interact with cytoplasmic proteins and are linked to IFs
+ others
What is the role of cadherins in morphogenesis?
Appearance and disappearance of specific cadherins drives morphogenesis
eg. in neurulation
What is morphogenesis?
Process by which anatomical structures are generated and organised.
What is neurulation?
Formation of the neural tube during embryogenesis at 3-4 weeks old
Explain how cadherins drive neurulation?
- Epithelial cells of ectoderm lose E-cadherin expression and aquire N-cadherin
- Cadherin change causes cells to segregate and the ectoderm to invaginate and pinch off to form part of the tube
- Cells that are a part of the neural tube lose N-cadherin and gain expression of Cadherin-7
- This allows neural crest cells to migrate from the neural tube.
- Two groups of migrating cells now re-express N-cadherins allowing them to aggregate and form peripheral ganglia
What does cadherin allow for neurulation to take place?
Because cadherins are differentially adhesive
What is Epithelial-Mesenchymal Transition (EMT)?
The process whereby epithelial cells lose their normal characteristics (adhesive, non-motile) and gain new characteristics (non-adhesive, motile)
How can EMT be induced?
Alterations in adhesion between cells
How can the loss of E-cadherin expression relate to cancer?
Loss of expression of Ecadherin and reduced cell adhesion can result in an EMT and:
• loss of histological structure
• increased motility
• increased invasiveness
Characteristics of cancer
How can the loss of E-cadherin expression promote invasion and metastasis?
- loss of E-cadherin mediated cell-cell adhesion allows invasion of the underlying connective tissue
- tumour cells are then able to enter the bloodstream by crossing the wall of a blood vessel
- these cells exit from the vessel elsewhere in the body and grow at a new site, forming a metastasis
What are focal adhesions?
Mediate cell0matrix adhesion
Found in epithelial or non-epithelial cells
Anchor actin microfilaments to the membrane
What are focal adhesions composed of?
Integrins - alpha and beta dimers
Structural proteins - Talin
Signalling proteins - Focal adhesion kinase FAK
What are integrins?
alpha and beta heterodimeric transmembrane receptors composed of 2 non-covalently linked subunits
18 alpha and 6 beta proteins combine forming 24 different dimers
What do almost all integrins link to?
microfilaments
What does the a6b6 integrin link to?
IFs in hemidesmosomes
What is the inactive and active states of integrins?
Inactive - alpha and beta chains are tightly folded
Active - Chains unfold into an extended confromation
How can activation of integrins be triggered?
Outside-in signalling: binding to a ligand (ECM protein)
Inside-out signalling: binding to talin
What is Outside-in signalling?
Integrins bind and switch to their active conformations when cells come into contact with ECM proteins
Increases integrin affinity for talin and enables them to recruit it to form to FA complex
FA complex is important for cell migration and cell growth
What is Inside-out signalling?
Platelets express aIIb3 integrin (inactive state)
When platelets come into contact with thrombin, Talin is activated and this activates aIIb3 integrin
Increases the affinity of aIIb3 for fibrinogen and leads to the formation of the platelet plug at the site of injury
What is Glanzmanns disease?
Mutation in either aII or B3 integrin chains preventing the interaction of platelets with fibrinogen at site of blood clots.
This is characterised by defective clotting and excessive bleeding.
