L21 - Cell Adhesion - Migration and Motility Flashcards
What are some examples of adhesion within the embryo?
Adhesion of sperm to the oocyte
Embryos go through a stage of compaction – begin to express adhesion molecules
- Embryo forms a morula
Egg has to implant in uterine wall by binding to endometrium wall
What are some examples of adhesion when forming the neural tube?
Cells in dorsal side of neural tube delaminate – neural crest cells
- Lose adhesion with neighbouring cells
- Migration involves adhering to various molecules
- They then aggregate again once they have finished migrating
What is an example of a classical cell aggregation experiment?
Sponges can reaggregate if broken apart
Cells self-organise based upon their adhesion
What happens if large reaggregations occur?
You see regionalisation?
What are L cells?
A cell line that expresses no cadherins?
What two things does transfection of L cells induce?
Homophilic sorting
- Some cells express E-cadherin some express N-cadherin
Graded sorting
- Some cells express high level of E-cadherin some express low levels
What are cadherins?
Integral membrane glycoproteins with 720-750 amino acids
How do cadherins interact?
Extracellular regions of two cadherins interact
- Ca binds to hinge regions to stabilise them
- Leads to conformational change and binding
- Allows them to interact with neighbouring cells
What does Ca control about cadherins?
Ca can control their levels of interaction
How do perpendicular arrays of cadherins act?
Perpendicular arrays of cadherins act like velcro
Arrays are localised to regions of the cell membrane
What are hypervariable protocadherins?
Evolved to form many different isoforms – via alternative splicing
Thought to have a role in specifying synapses
Though to have a role in neurite self-avoidance
What are the two different subtypes of cadherins?
Classical
- E-cadherin
- Found in many epithelia
- Involved in adheren junctions
Non-classical - more specific functions
- Cadherin 23
- Found in the inner ear
Cadherin family structure
Most have single transmembrane domains but can have multiple
All have repeated extracellular domains – some have added extra molecules
What do catenins connect?
Connect cadherins to actin filaments
What are the role of catenins?
Signalling
Building junctions
How are catenins involved in signalling?
B catenin can regulate proliferation via c-myc
How are catenins involved in building junctions?
- Myosin / actin interaction
- Exposes vinculin binding site
- Cross-linking in more actin filaments
- Myosin pulls on actin extending a-catenin
- This pulls on the attached cadherin which is attached to another cadherin
How do Rho mutants affect the actin cytoskeleton?
Constitutively active Rho activation leads to stress fibre formation
Changes the cell shape
What cadherin is expressed in the early embryo?
E-cadherin
When is E-cadherin lost in the embryo?
Newly formed mesoderm cells lose E-cadherin – mesoderm needs to migrate inwards
What is E-cadherin replaced by in the neural tube?
N-cadherin replaces E-cadherin in the neural tube
What happens to neural crest cells during migration?
Complex changes in neural crest cells during migration
Express cadherin 7 when they first migrate
Selectin structure
Intracellular domain - anchored to actin (like which cadherins)
Extracellular domain – many repeated domains and unique domains at the end
What s the role of selectins?
Major role in neutrophil trapping
- Cells become adhered to outside wall of blood vessel
- Cells keep rolling slowly - selectin dependent
- Once cells stop rolling they move between endothelial cells into tissue – integrin dependent
What do selectins bind to?
Ca dependent binding
Bind carbohydrates on neighbouring cells
Where do selectins bind?
Cell surface - single transmembrane domain
Ca independent CAMs structure?
Can be extracellular or transmembrane
What is the major part of the Ca independent CAMs family?
Neural cell adhesion molecules (N-CAMs)
What do Ca independent CAMs mediate?
Homophilic binding
Interactions with ECM and between different cells
Where do Ca independent CAMs come from?
Arise from alternative splicing and can undergo post translational glycosylation
What do variable polysialic acid concentrations in Ca independent CAMs do?
More N-CAMS in immature tissue in the neural tube
Means there is less adhesion
Summary
Expression of CAM’s is regulated
CAM expression correlates with migration and aggregation
CAM expression may delineate regions of a cell’s membrane
